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1
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Taher M, Jalali H, Kouchesfehani HM. Small extracellular vesicles derived from Nrf2-stimulated bone marrow mesenchymal stem cells ameliorated the testis damage and fertility disorder in doxorubicin-treated mice. Reprod Toxicol 2025; 132:108847. [PMID: 39894000 DOI: 10.1016/j.reprotox.2025.108847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 01/25/2025] [Accepted: 01/27/2025] [Indexed: 02/04/2025]
Abstract
Bone marrow mesenchymal/stromal stem cell (BMSC)-derived small extracellular vesicles (sEVs) are promising therapeutic agents owing to their low immunogenicity and ability to cross biological barriers. Doxorubicin (DOX), a common chemotherapeutic agent, damages testicular tissue. This study aimed to enhance the antioxidant activity of sEVs by activating the Nrf2 gene in BMSCs and evaluate their therapeutic potential for DOX-induced fertility disorders. Testicular damage was induced by DOX in NMRI mice. BMSCs from Wistar rats were treated with Bardoxolone methyl (BaMet) to upregulate Nrf2. The sEVs were isolated through differential ultracentrifugation and validated for size, morphology, and protein expression. The antioxidant activity was assessed using specific kits. sEVs containing 10 μg of proteins were injected intravenously into DOX-injured mice. After 35 days, the testes were collected for histopathological, hormonal, and immunological analyses, along with the evaluation of sperm parameters. Male and female mice were paired to determine the pregnancy rates. BaMet-sEVs exhibited higher antioxidant activity and significantly improved serum testosterone levels, testicular cell populations, sperm viability, and motility in DOX-injured mice. In addition, BaMet-sEVs treatment enhanced fertility and increased the number of offspring. This study demonstrated the effectiveness of BaMet-sEVs in mitigating DOX-induced testicular damage.
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Affiliation(s)
- Maryam Taher
- Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
| | - Hanieh Jalali
- Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
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2
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Fomichova O, Oliveira PF, Bernardino RL. Exploring the interplay between inflammation and male fertility. FEBS J 2024. [PMID: 39702986 DOI: 10.1111/febs.17366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 10/02/2024] [Accepted: 12/10/2024] [Indexed: 12/21/2024]
Abstract
Male fertility results from a complex interplay of physiological, environmental, and genetic factors. It is conditioned by the properly developed anatomy of the reproductive system, hormonal regulation balance, and the interplay between different cell populations that sustain an appropriate and functional environment in the testes. Unfortunately, the mechanisms sustaining male fertility are not flawless and their perturbation can lead to infertility. Inflammation is one of the factors that contribute to male infertility. In the testes, it can be brought on by varicocele, obesity, gonadal infections, leukocytospermia, physical obstructions or traumas, and consumption of toxic substances. As a result of prolonged or untreated inflammation, the testicular resident cells that sustain spermatogenesis can suffer DNA damage, lipid and protein oxidation, and mitochondrial dysfunction consequently leading to loss of function in affected Sertoli cells (SCs) and Leydig cells (LCs), and the formation of morphologically abnormal dysfunctional sperm cells that lay in the basis of male infertility and subfertility. This is due mainly to the production and secretion of pro-inflammatory mediators, including cytokines, chemokines, and reactive oxygen species (ROS) by local immune cells (macrophages, lymphocytes T, mast cells) and tissue-specific cells [SCs, LCs, peritubular myoid cells (PMCs) and germ cells (GCs)]. Depending on the location, duration, and intensity of inflammation, these mediators can exert their toxic effect on different elements of the testes. In this review, we discuss the most prevalent inflammatory factors that negatively affect male fertility and describe the different ways inflammation can impair male reproductive function.
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Affiliation(s)
- Oleksandra Fomichova
- UMIB - Unit for Multidisciplinary Research in Biomedicine, ICBAS - School of Medicine and Biomedical Sciences, University of Porto, Portugal
| | - Pedro F Oliveira
- LAQV-REQUIMTE and Department of Chemistry, University of Aveiro, Portugal
| | - Raquel L Bernardino
- UMIB - Unit for Multidisciplinary Research in Biomedicine, ICBAS - School of Medicine and Biomedical Sciences, University of Porto, Portugal
- Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, Portugal
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3
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Min CG, Ma X, Wang YC, Zhong CK, Yuan CS, Zhang KY, Zhan CL, Hou SK, Wang XH, Wang J, Zhao J, Fang Y, Liu HY, Ding H, Guo J, Lu WF. The effects of repeated freezing and thawing on bovine sperm morphometry and function. Cryobiology 2024; 115:104892. [PMID: 38593909 DOI: 10.1016/j.cryobiol.2024.104892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 03/14/2024] [Accepted: 04/02/2024] [Indexed: 04/11/2024]
Abstract
Refreezing the remaining genetic resources after in vitro fertilization (IVF) can conserve genetic materials. However, the precise damage inflicted by repeated freezing and thawing on bovine sperm and its underlying mechanism remain largely unexplored. Thus, this study investigates the impact of repeated freeze-thaw cycles on sperm. Our findings indicate that such cycles significantly reduce sperm viability and motility. Furthermore, the integrity of the sperm plasma membrane and acrosome is compromised during this process, exacerbating the advanced apoptosis triggered by oxidative stress. Additionally, transmission electron microscopy exposed severe damage to the plasma membranes of both the sperm head and tail. Notably, the "9 + 2" structure of the tail was disrupted, along with a significant decrease in the level of the axonemal protein DNAH10, leading to reduced sperm motility. IVF outcomes revealed that repeated freeze-thaw cycles considerably impair sperm fertilization capability, ultimately reducing the blastocyst rate. In summary, our research demonstrates that repeated freeze-thaw cycles lead to a decline in sperm viability and motility, attributed to oxidative stress-induced apoptosis and DNAH10-related dynamic deficiency. As a result, the utility of semen is compromised after repeated freezing.
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Affiliation(s)
- Chang-Guo Min
- Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, Jilin, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China
| | - Xin Ma
- Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, Jilin, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China
| | - Yu-Chan Wang
- Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, Jilin, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China
| | - Cheng-Kun Zhong
- Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, Jilin, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China
| | - Chong-Shan Yuan
- Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, Jilin, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China
| | - Kai-Yan Zhang
- Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, Jilin, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China
| | - Cheng-Lin Zhan
- Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, Jilin, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China
| | - Sheng-Kui Hou
- Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, Jilin, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China
| | - Xin-Hai Wang
- Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, Jilin, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China
| | - Jun Wang
- Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, Jilin, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China
| | - Jing Zhao
- Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, Jilin, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China
| | - Yi Fang
- Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, Jilin, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China
| | - Hong-Yu Liu
- Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, Jilin, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China
| | - He Ding
- Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, Jilin, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China
| | - Jing Guo
- Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, Jilin, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China.
| | - Wen-Fa Lu
- Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, Jilin, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China.
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Mori Y, Terasaki M, Osaka N, Fujikawa T, Yashima H, Saito T, Kataoka Y, Ohara M, Higashimoto Y, Matsui T, Yamagishi SI. DNA Aptamer Raised against Advanced Glycation End Products Improves Sperm Concentration, Motility, and Viability by Suppressing Receptors for Advanced Glycation End Product-Induced Oxidative Stress and Inflammation in the Testes of Diabetic Mice. Int J Mol Sci 2024; 25:5947. [PMID: 38892134 PMCID: PMC11172898 DOI: 10.3390/ijms25115947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 05/21/2024] [Accepted: 05/28/2024] [Indexed: 06/21/2024] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a risk factor for male infertility, but the underlying molecular mechanisms remain unclear. Advanced glycation end products (AGEs) are pathogenic molecules for diabetic vascular complications. Here, we investigated the effects of the DNA aptamer raised against AGEs (AGE-Apt) on testicular and sperm abnormalities in a T2DM mouse model. KK-Ay (DM) and wild-type (non-DM) 4- and 7-week-old male mice were sacrificed to collect the testes and spermatozoa for immunofluorescence, RT-PCR, and histological analyses. DM and non-DM 7-week-old mice were subcutaneously infused with the AGE-Apt or control-aptamer for 6 weeks and were then sacrificed. Plasma glucose, testicular AGEs, and Rage gene expression in 4-week-old DM mice and plasma glucose, testicular AGEs, oxidative stress, and pro-inflammatory gene expressions in 7-week-old DM mice were higher than those in age-matched non-DM mice, the latter of which was associated with seminiferous tubular dilation. AGE-Apt did not affect glycemic parameters, but it inhibited seminiferous tubular dilation, reduced the number of testicular macrophages and apoptotic cells, and restored the decrease in sperm concentration, motility, and viability of 13-week-old DM mice. Our findings suggest that AGEs-Apt may improve sperm abnormality by suppressing AGE-RAGE-induced oxidative stress and inflammation in the testes of DM mice.
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Affiliation(s)
- Yusaku Mori
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Anti-Glycation Research Section, Showa University Graduate School of Medicine, Shinagawa 142-8555, Tokyo, Japan
| | - Michishige Terasaki
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University Graduate School of Medicine, Shinagawa 142-8555, Tokyo, Japan; (M.T.); (S.-i.Y.)
| | - Naoya Osaka
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University Graduate School of Medicine, Shinagawa 142-8555, Tokyo, Japan; (M.T.); (S.-i.Y.)
| | - Tomoki Fujikawa
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University Graduate School of Medicine, Shinagawa 142-8555, Tokyo, Japan; (M.T.); (S.-i.Y.)
| | - Hironori Yashima
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University Graduate School of Medicine, Shinagawa 142-8555, Tokyo, Japan; (M.T.); (S.-i.Y.)
| | - Tomomi Saito
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University Graduate School of Medicine, Shinagawa 142-8555, Tokyo, Japan; (M.T.); (S.-i.Y.)
| | - Yurie Kataoka
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University Graduate School of Medicine, Shinagawa 142-8555, Tokyo, Japan; (M.T.); (S.-i.Y.)
| | - Makoto Ohara
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University Graduate School of Medicine, Shinagawa 142-8555, Tokyo, Japan; (M.T.); (S.-i.Y.)
| | - Yuichiro Higashimoto
- Department of Chemistry, Kurume University School of Medicine, Kurume 830-0011, Fukuoka, Japan;
| | - Takanori Matsui
- Department of Bioscience and Biotechnology, Fukui Prefectural University, Eiheiji 910-1195, Fukui, Japan
| | - Sho-ichi Yamagishi
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University Graduate School of Medicine, Shinagawa 142-8555, Tokyo, Japan; (M.T.); (S.-i.Y.)
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5
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Henkel R. Leukocytospermia and/or Bacteriospermia: Impact on Male Infertility. J Clin Med 2024; 13:2841. [PMID: 38792382 PMCID: PMC11122306 DOI: 10.3390/jcm13102841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 05/07/2024] [Accepted: 05/07/2024] [Indexed: 05/26/2024] Open
Abstract
Infertility is a globally underestimated public health concern affecting almost 190 million people, i.e., about 17.5% of people during their lifetime, while the prevalence of male factor infertility is about 7%. Among numerous other causes, the prevalence of male genital tract infections reportedly ranges between 10% and 35%. Leukocytospermia is found in 30% of infertile men and up to 20% in fertile men. Bacterial infections cause an inflammatory response attracting leukocytes, which produce reactive oxygen species (ROS) and release cytokines, both of which can cause damage to sperm, rendering them dysfunctional. Although leukocytospermia and bacteriospermia are both clinical conditions that can negatively affect male fertility, there is still debate about their impact on assisted reproduction outcomes and management. According to World Health Organization (WHO) guidelines, leukocytes should be determined by means of the Endtz test or with monoclonal antibodies against CD15, CD68 or CD22. The cut-off value proposed by the WHO is 1 × 106 peroxidase-positive cells/mL. For bacteria, Gram staining and semen culture are regarded as the "gold standard", while modern techniques such as PCR and next-generation sequencing (NGS) are allowing clinicians to detect a wider range of pathogens. Whereas the WHO manual does not specify a specific value as a cut-off for bacterial contamination, several studies consider semen samples with more than 103 colony-forming units (cfu)/mL as bacteriospermic. The pathogenic mechanisms leading to sperm dysfunction include direct interaction of bacteria with the male germ cells, bacterial release of spermatotoxic substances, induction of pro-inflammatory cytokines and ROS, all of which lead to oxidative stress. Clinically, bacterial infections, including "silent" infections, are treatable, with antibiotics being the treatment of choice. Yet, non-steroidal antiphlogistics or antioxidants should also be considered to alleviate inflammatory lesions and improve semen quality. In an assisted reproduction set up, sperm separation techniques significantly reduce the bacterial load in the semen. Nonetheless, contamination of the semen sample with skin commensals should be prevented by applying relevant hygiene techniques. In patients where leukocytospermia is detected, the causes (e.g. infection, inflammation, varicocele, smoking, etc.) of the leukocyte infiltration have to be identified and addressed with antibiotics, anti-inflammatories or antioxidants in cases where high oxidative stress levels are detected. However, no specific strategy is available for the management of leukocytospermia. Therefore, the relationship between bacteriospermia and leukocytospermia as well as their specific impact on functional sperm parameters and reproductive outcome variables such as fertilization or clinical pregnancy must be further investigated. The aim of this narrative review is to provide an update on the current knowledge on leukocytospermia and bacteriospermia and their impact on male fertility.
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Affiliation(s)
- Ralf Henkel
- LogixX Pharma Ltd., Merlin House, Brunel Road, Theale, Reading RG7 4AB, UK;
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London W12 0HS, UK
- Department of Medical Bioscience, University of the Western Cape, Bellville 7535, South Africa
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Ma JY, Xia TJ, Li S, Yin S, Luo SM, Li G. Germline cell de novo mutations and potential effects of inflammation on germline cell genome stability. Semin Cell Dev Biol 2024; 154:316-327. [PMID: 36376195 DOI: 10.1016/j.semcdb.2022.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 11/05/2022] [Accepted: 11/06/2022] [Indexed: 11/13/2022]
Abstract
Uncontrolled pathogenic genome mutations in germline cells might impair adult fertility, lead to birth defects or even affect the adaptability of a species. Understanding the sources of DNA damage, as well as the features of damage response in germline cells are the overarching tasks to reduce the mutations in germline cells. With the accumulation of human genome data and genetic reports, genome variants formed in germline cells are being extensively explored. However, the sources of DNA damage, the damage repair mechanisms, and the effects of DNA damage or mutations on the development of germline cells are still unclear. Besides exogenous triggers of DNA damage such as irradiation and genotoxic chemicals, endogenous exposure to inflammation may also contribute to the genome instability of germline cells. In this review, we summarized the features of de novo mutations and the specific DNA damage responses in germline cells and explored the possible roles of inflammation on the genome stability of germline cells.
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Affiliation(s)
- Jun-Yu Ma
- Fertility Preservation Lab, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, China.
| | - Tian-Jin Xia
- Fertility Preservation Lab, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, China; College of Life Sciences, Qingdao Agricultural University, Qingdao, China
| | - Shuai Li
- Center for Clinical Epidemiology and Methodology, Guangdong Second Provincial General Hospital, Guangzhou, China
| | - Shen Yin
- College of Life Sciences, Qingdao Agricultural University, Qingdao, China.
| | - Shi-Ming Luo
- Fertility Preservation Lab, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, China.
| | - Guowei Li
- Center for Clinical Epidemiology and Methodology, Guangdong Second Provincial General Hospital, Guangzhou, China.
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Olarotimi OJ, Gbore FA, Adu OA, Oloruntola OD, Jimoh OA. Ameliorative effects of Sida acuta and vitamin C on serum DNA damage, pro-inflammatory and anti-inflammatory cytokines in roosters fed aflatoxin B 1 contaminated diets. Toxicon 2023; 236:107330. [PMID: 37944826 DOI: 10.1016/j.toxicon.2023.107330] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 10/14/2023] [Accepted: 10/30/2023] [Indexed: 11/12/2023]
Abstract
The ameliorative effects of Sida acuta leaf meal (SALM) and vitamin C on the serum pro-inflammatory and anti-inflammatory cytokines as well as DNA damage of cocks fed aflatoxin B1 (AFB1) contaminated diets were examined. The experiment was a completely randomized design with a total of 250 sexually mature Isa White cocks aged 24 weeks, randomly allotted into five experimental diets; each diet contained 5 replicates with 10 roosters. The diets were A (control/basal diet), B (A + 1 mg/kg AFB1), C (B + 200 mg/kg vitamin C), D (B + 2.5 g/kg SALM) and E (B + 5.0 g/kg SALM). Fresh and clean water was also provided for the whole experimental period of twelve weeks. Inclusion of 1 mg/kg AFB1 without vitamin C or SALM increased TNF-α and IL-1β as well as 8-OHdG and NF-κB in the serum significantly (P < 0.05) among the cocks on diet B. However, the fortification of AFB1 contaminated diets with vitamin C and SALM depressed serum TNF-α, IL-1β, 8-OHdG and NF-κB concentrations of the cocks significantly (P < 0.05). Conversely, serum IL-4 and IL-10 in birds given 1 mg/kg AFB1 without vitamin C or SALM decreased significantly (P < 0.05) in comparison with the roosters on the control. However, improvements (P < 0.05) in IL-4 and IL-10 concentrations with corresponding reduction (P < 0.05) in TNF-α, IL-1β, 8-OHdG and NF-κB concentrations were recorded among cocks fed Diets C, D and E, respectively. Therefore, dietary addition of SALM at the level used in this study was beneficial and has comparable effects with inorganic antioxidant (C vitamin) by significantly reducing the inflammatory cytokines and oxidative damage biomarkers as well as enhancing the anti-inflammatory cytokines thereby promoting the health status of the cocks fed AFB1 contaminated ration.
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Affiliation(s)
- Olumuyiwa Joseph Olarotimi
- Department of Animal Science, Faculty of Agriculture, Adekunle Ajasin University, P.M.B. 001, Akungba-Akoko, Nigeria.
| | - Francis Ayodeji Gbore
- Department of Animal Science, Faculty of Agriculture, Adekunle Ajasin University, P.M.B. 001, Akungba-Akoko, Nigeria
| | - Olufemi Adesanya Adu
- Department of Animal Production and Health, School of Agriculture and Agricultural Technology, Federal University of Technology, P.M.B. 704, Akure, Nigeria
| | - Olugbenga David Oloruntola
- Department of Animal Science, Faculty of Agriculture, Adekunle Ajasin University, P.M.B. 001, Akungba-Akoko, Nigeria
| | - Olatunji Abubakar Jimoh
- Department of Agricultural Technology, The Federal Polytechnic Ado-Ekiti, Ekiti State, Nigeria
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8
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Fan S, Zhao Y, Zhang Z, Wang H, Hou Y, Bai S, Liu R, Xu B. Effect of leukocytes on semen quality in men from primary and secondary infertile couples: A cross-sectional study. Health Sci Rep 2023; 6:e1683. [PMID: 38028702 PMCID: PMC10630749 DOI: 10.1002/hsr2.1683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Revised: 10/06/2023] [Accepted: 10/19/2023] [Indexed: 12/01/2023] Open
Abstract
Background and Aims Leukocytospermia (LCS) is a known cause of male infertility. However, the relationship between seminal leukocytes and semen quality among infertile couples remains controversial. This study aims to investigate the association between semen quality and LCS in male partners of infertile couples. Methods Semen samples were collected from 512 men who asked for a fertility evaluation in a reproductive center in China. Seminal leukocytes were counted following peroxidase staining with benzidine. Other semen parameters were compared in subfertile men with and without LCS. Results Poor semen quality (e.g., low semen volume, sperm concentration, and sperm progressive/total motility) was observed among men with LCS compared to those without LCS. Men with LCS had a higher risk of low sperm progressive motility (OR = 0.99, 95% CI = 0.98-0.99, p = 0.02) and total motility (OR = 0.99, 95% CI = 0.98-0.99, p = 0.02), even after adjustment for potential confounders (both OR = 0.99, 95% CI = 0.98-0.99, p = 0.03). Lower sperm viability was observed in LCS from male partners of secondary couples, while no significant difference in semen parameters was found between men with and without LCS in male partners of primary infertile couples. Low sperm motility and viability were associated with LCS in men from secondary infertile couples after adjusting for confounders (OR = 0.97, 95% CI = 0.95-0.99, p = 0.04; OR = 0.94, 95% CI = 0.89-0.99, p = 0.04, respectively). Conclusions Our findings indicate that a higher risk of abnormal semen parameters was correlated with an increased number of leukocytes in men from secondary infertile couples.
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Affiliation(s)
- Shiwei Fan
- Reproductive and Genetic Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina
| | - Yuanqi Zhao
- Reproductive and Genetic Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina
- Wannan Medical CollegeWuhuAnhuiChina
| | - Zeling Zhang
- Reproductive and Genetic Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina
| | - Huiru Wang
- Reproductive and Genetic Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina
| | - Yifu Hou
- Center for Reproductive MedicineTraditional Chinese Hospital of LuAnLu'anAnhuiChina
| | - Shun Bai
- Reproductive and Genetic Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina
| | - Ran Liu
- Reproductive and Genetic Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina
| | - Bo Xu
- Reproductive and Genetic Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina
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9
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Odetayo AF, Adeyemi WJ, Olayaki LA. In vivo exposure to bisphenol F induces oxidative testicular toxicity: role of Erβ and p53/Bcl-2 signaling pathway. FRONTIERS IN REPRODUCTIVE HEALTH 2023; 5:1204728. [PMID: 37601897 PMCID: PMC10433915 DOI: 10.3389/frph.2023.1204728] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 07/07/2023] [Indexed: 08/22/2023] Open
Abstract
Introduction Bisphenol F (BPF), an alternative to bisphenol A has been implicated as a gonadotoxic substance. BPF has been shown to induce hormonal imbalance and testicular oxidative damage. However, the mechanism associated with BPF-induced testicular toxicity has not been fully explored. This study was designed to explore the role of tumor protein (p53)/ B-cell lymphoma 2 (BCl-2) signaling and oestrogen receptor beta (Erβ) in BPF-induced testicular toxicity. Methods Male Wistar rats were randomized into control (Cntrl), BPF-treated (10, 30, and 50 mg/kg for low dose (BPF-L), medium dose (BPF-M), and high dose (BPF-H) respectively), and BPF-treated recovery (Cntrl-R, BPF-L-R, BPF-M-R, and BPF-H-R). The administration was via gavage and lasted for 28 days and the animals in the recovery groups were allowed 28-days exposure free period for recovery from BPF exposure. Results BPF resulted in the distortion of the testicular histoarchitecture, which was accompanied by a significant rise in testicular gamma-lutamyl transferase and lactate dehydrogenase activities but a decline in sorbitol dehydrogenase activities. Also, BPF caused a significant reduction in plasma gonadotropin-releasing hormone, luteinising hormone, follicle-stimulating hormone, and testosterone, which was associated with the downregulation of testicular 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase activities. Furthermore, BPF induced testicular inflammation, redox imbalance, and apoptosis, accompanied by distortion in p53/BCl-2 signaling and overexpression of Erβ. Again, the observed toxic effects of BPF were dose-dependent and not completely reversed by BPF cessation. Discussion Bisphenol F induced gonadotoxicity by distorting p53/BCl2 signaling and the expression of Erβ. These observed alterations were not completely reversed after the cessation of BPF exposure.
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Affiliation(s)
- Adeyemi Fatai Odetayo
- Physiology Department, University of Ilorin, Ilorin, Nigeria
- Physiology Department, Federal University of Health Sciences, Ila Orangun, Nigeria
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Castiglione R, Vivacqua A, Santoro M, De Rose D, Peluso G, Panza S, Aquila S, D'Agata R. Glucagon-like Peptide-1 Acts as Signaling Mediator to Modulate Human Sperm Performance via Targeting Akt, JNK and IRS-1 Cell Signaling Cascades: Novel Insights into Sperm Physiopathology. J Clin Med 2023; 12:jcm12113844. [PMID: 37298039 DOI: 10.3390/jcm12113844] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 05/19/2023] [Accepted: 06/01/2023] [Indexed: 06/12/2023] Open
Abstract
Recent evidence suggests that the male gonad is a potential target of glucagon-like peptide-1 (GLP-1). We investigated the effects of glucagon-like peptide-1 (GLP-1) on sperm function and the molecular mechanisms through which it may act. Semen samples of healthy men were incubated in the presence or absence of a GLP-1 mimetic analog, exendin-4 (Exe). In a different analysis, sperm were exposed to tumor necrosis factor (TNF-α) alone and, in some tubes, TNF-α was added after previous exposure to exendin-4 (Exe). Sperm parameters and protein-kinase B (p-Akt), insulin receptor substrate-1 (p-IRS-1 Ser312), and c Jun N-terminal protein kinase (p-JNK Thr183/Tyr185) were considered and evaluated. Sperm parameters, when incubated for 4 h in a simple defined balanced salt solution lacking protein, declined progressively with incubation time. The maximum decline was associated with a significant decrease in phosphorylated protein kinase B (p-Akt), concomitantly to an increase in insulin receptor substrate-1 (p-IRS-1 Ser312) and c Jun N-terminal protein kinase (p-JNK Thr183/Tyr185). Preincubation with exendin-4 (Exe) prevented this decline and maintained sperm motility (progressive-PM and total-TM). TNF-α exposure resulted in decreased sperm motility (PM and TM) and viability (V) in a concentration-dependent manner. Exe addition attenuated this TNF-α negative effect on sperm parameters. Glucagon-like peptide-1 (GLP-1) also acts by reducing levels of the "negative" kinases p-IRS-1Ser312 and p-JNK. An imbalance involving these three kinases in sperm, as it occurs in somatic cells, is a novel scenario that may participate in sperm physiopathology.
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Affiliation(s)
- Roberto Castiglione
- Department of Experimental and Clinical Medicine, University of Catania, 95123 Catania, Italy
| | - Adele Vivacqua
- Department of Pharmacy and Science of Health and Nutrition, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy
- Centro Sanitario, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy
| | - Marta Santoro
- Department of Pharmacy and Science of Health and Nutrition, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy
- Centro Sanitario, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy
| | - Daniela De Rose
- Department of Pharmacy and Science of Health and Nutrition, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy
- Centro Sanitario, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy
| | - Giuseppina Peluso
- Unit of Physiophatology of Reproduction, Annunziata Hospital, 87100 Cosenza, Italy
| | - Salvatore Panza
- Department of Pharmacy and Science of Health and Nutrition, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy
- Centro Sanitario, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy
| | - Saveria Aquila
- Department of Pharmacy and Science of Health and Nutrition, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy
- Centro Sanitario, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy
| | - Rosario D'Agata
- Department of Experimental and Clinical Medicine, University of Catania, 95123 Catania, Italy
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Kumar L, Dwivedi M, Jain N, Shete P, Solanki S, Gupta R, Jain A. The Female Reproductive Tract Microbiota: Friends and Foe. Life (Basel) 2023; 13:1313. [PMID: 37374096 DOI: 10.3390/life13061313] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Revised: 05/26/2023] [Accepted: 05/29/2023] [Indexed: 06/29/2023] Open
Abstract
We do not seem to be the only owner of our body; it houses a large population of microorganisms. Through countless years of coevolution, microbes and hosts have developed complex relationships. In the past few years, the impact of microbial communities on their host has received significant attention. Advanced molecular sequencing techniques have revealed a remarkable diversity of the organ-specific microbiota populations, including in the reproductive tract. Currently, the goal of researchers has shifted to generate and perceive the molecular data of those hidden travelers of our body and harness them for the betterment of human health. Recently, microbial communities of the lower and upper reproductive tract and their correlation with the implication in reproductive health and disease have been extensively studied. Many intrinsic and extrinsic factors influences the female reproductive tract microbiota (FRTM) that directly affects the reproductive health. It is now believed that FRTM dominated by Lactobacilli may play an essential role in obstetric health beyond the woman's intimate comfort and well-being. Women with altered microbiota may face numerous health-related issues. Altered microbiota can be manipulated and restored to their original shape to re-establish normal reproductive health. The aim of the present review is to summarize the FRTM functional aspects that influence reproductive health.
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Affiliation(s)
- Lokesh Kumar
- Genus Breeding India Pvt Ltd., Pune 411005, Maharashtra, India
| | - Monika Dwivedi
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra 835215, Jharkhand, India
| | - Natasha Jain
- Department of Biotechnology, Chaudhary Charan Singh University, Meerut 250001, Uttar Pradesh, India
| | - Pranali Shete
- Department of Microbiology, Smt. CHM College, University of Mumbai, Ulhasnagar 421003, Maharashtra, India
| | - Subhash Solanki
- Genus Breeding India Pvt Ltd., Pune 411005, Maharashtra, India
| | - Rahul Gupta
- Genus Breeding India Pvt Ltd., Pune 411005, Maharashtra, India
| | - Ashish Jain
- Department of Microbiology, Smt. CHM College, University of Mumbai, Ulhasnagar 421003, Maharashtra, India
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Petricca S, Carnicelli V, Luzi C, Cinque B, Celenza G, Iorio R. Oxidative Stress, Cytotoxic and Inflammatory Effects of Azoles Combinatorial Mixtures in Sertoli TM4 Cells. Antioxidants (Basel) 2023; 12:1142. [PMID: 37371872 DOI: 10.3390/antiox12061142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 05/18/2023] [Accepted: 05/22/2023] [Indexed: 06/29/2023] Open
Abstract
Triazole and imidazole fungicides are an emerging class of contaminants with an increasing and ubiquitous presence in the environment. In mammals, their reproductive toxicity has been reported. Concerning male reproduction, a combinatorial activity of tebuconazole (TEB; triazole fungicide) and econazole (ECO; imidazole compound) in inducing mitochondrial impairment, energy depletion, cell cycle arrest, and the sequential activation of autophagy and apoptosis in Sertoli TM4 cells (SCs) has recently been demonstrated. Given the strict relationship between mitochondrial activity and reactive oxygen species (ROS), and the causative role of oxidative stress (OS) in male reproductive dysfunction, the individual and combined potential of TEB and ECO in inducing redox status alterations and OS was investigated. Furthermore, considering the impact of cyclooxygenase (COX)-2 and tumor necrosis factor-alpha (TNF-α) in modulating male fertility, protein expression levels were assessed. In the present study, we demonstrate that azoles-induced cytotoxicity is associated with a significant increase in ROS production, a drastic reduction in superoxide dismutase (SOD) and GSH-S-transferase activity levels, and a marked increase in the levels of oxidized (GSSG) glutathione. Exposure to azoles also induced COX-2 expression and increased TNF-α production. Furthermore, pre-treatment with N-acetylcysteine (NAC) mitigates ROS accumulation, attenuates COX-2 expression and TNF-α production, and rescues SCs from azole-induced apoptosis, suggesting a ROS-dependent molecular mechanism underlying the azole-induced cytotoxicity.
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Affiliation(s)
- Sabrina Petricca
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100 L'Aquila, Italy
| | - Veronica Carnicelli
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100 L'Aquila, Italy
| | - Carla Luzi
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100 L'Aquila, Italy
| | - Benedetta Cinque
- Department of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, 67100 L'Aquila, Italy
| | - Giuseppe Celenza
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100 L'Aquila, Italy
| | - Roberto Iorio
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100 L'Aquila, Italy
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Cannarella R, Mancuso F, Barone N, Arato I, Lilli C, Bellucci C, Musmeci M, Luca G, La Vignera S, Condorelli RA, Calogero AE. Effects of Follicle-Stimulating Hormone on Human Sperm Motility In Vitro. Int J Mol Sci 2023; 24:ijms24076536. [PMID: 37047508 PMCID: PMC10095528 DOI: 10.3390/ijms24076536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 03/17/2023] [Accepted: 03/29/2023] [Indexed: 04/03/2023] Open
Abstract
To evaluate whether the follicle-stimulating hormone (FSH) receptor (FSHR) is expressed in human spermatozoa and the effects of FSH incubation on sperm function. Twenty-four Caucasian men were recruited. Thirteen patients had asthenozoospermia, and the remaining 11 had normal sperm parameters (controls). After confirming FSHR expression, spermatozoa from patients and controls were incubated with increasing concentrations of human purified FSH (hpFSH) to reassess FSHR expression and localization and to evaluate progressive and total sperm motility, the mitochondrial membrane potential, and protein kinase B (AKT) 473 and 308 phosphorylation. FSHR is expressed in the post-acrosomal segment, neck, midpiece, and tail of human spermatozoa. Its localization does not differ between patients and controls. Incubation with hpFSH at a concentration of 30 mIU/mL appeared to increase FSHR expression mainly in patients. Incubation of human spermatozoa with hpFSH overall resulted in an overall deterioration of both progressive and total motility in patients and controls and worse mitochondrial function only in controls. Finally, incubation with FSH increased AKT473/tubulin phosphorylation to a greater extent than AKT308. FSHR is expressed in the post-acrosomal region, neck, midpiece, and tail of human spermatozoa. Contrary to a previous study, we report a negative effect of FSH on sperm motility and mitochondrial function. FSH also activates the AKT473 signaling pathway.
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Tvrdá E, Ďuračka M, Benko F, Kováčik A, Lovíšek D, Gálová E, Žiarovská J, Schwarzová M, Kačániová M. Ejaculatory Abstinence Affects the Sperm Quality in Normozoospermic Men-How Does the Seminal Bacteriome Respond? Int J Mol Sci 2023; 24:ijms24043503. [PMID: 36834909 PMCID: PMC9963725 DOI: 10.3390/ijms24043503] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/01/2023] [Accepted: 02/04/2023] [Indexed: 02/12/2023] Open
Abstract
This study was designed to describe bacterial profiles of ejaculates collected following a long and short ejaculatory abstinence set in the context of changes in the conventional, oxidative, and immunological characteristics of semen. Two specimens were collected in succession from normozoospermic men (n = 51) following 2 days and 2 h, respectively. Semen samples were processed and analyzed according to the World Health Organization (WHO) 2021 guidelines. Afterwards, sperm DNA fragmentation, mitochondrial function, levels of reactive oxygen species (ROS), total antioxidant capacity, and oxidative damage to sperm lipids and proteins were evaluated in each specimen. Selected cytokine levels were quantified using the ELISA method. Bacterial identification by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry revealed that samples collected following two days of abstinence presented with a higher bacterial load and diversity, and a greater prevalence of potentially uropathogenic bacteria including Escherichia coli, Staphylococcus aureus and Enterococcus faecalis. Only staphylococci and Escherichia coli remained present in specimens obtained after 2 h of abstinence. Whilst all samples accomplished the criteria set by WHO, a significantly higher motility (p < 0.05), membrane integrity (p < 0.05), mitochondrial membrane potential (p < 0.05), and DNA integrity (p < 0.0001) were detected following 2 h of ejaculatory abstinence. On the other hand, significantly higher ROS levels (p < 0.001), protein oxidation (p < 0.001), and lipid peroxidation (p < 0.01) accompanied by significantly higher concentrations of tumor necrosis factor alpha (p < 0.05), interleukin-6 (p < 0.01), and interferon gamma (p < 0.05) were observed in specimens collected after two days of abstinence. It may be summarized that shorter ejaculatory abstinence does not compromise sperm quality in normozoospermic men, while it contributes to a decreased occurrence of bacteria in semen which is accompanied by a lower probability of damage to spermatozoa by ROS or pro-inflammatory cytokines.
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Affiliation(s)
- Eva Tvrdá
- Institute of Biotechnology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, 94976 Nitra, Slovakia
- Correspondence: ; Tel.: +421-37-641-4918
| | - Michal Ďuračka
- AgroBioTech Research Centre, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, 94976 Nitra, Slovakia
| | - Filip Benko
- Institute of Applied Biology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, 94976 Nitra, Slovakia
| | - Anton Kováčik
- Institute of Applied Biology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, 94976 Nitra, Slovakia
| | - Daniel Lovíšek
- Department of Genetics, Faculty of Natural Sciences, Comenius University, Ilkovičova 6, Mlynská Dolina, 84215 Bratislava, Slovakia
| | - Eliška Gálová
- Department of Genetics, Faculty of Natural Sciences, Comenius University, Ilkovičova 6, Mlynská Dolina, 84215 Bratislava, Slovakia
| | - Jana Žiarovská
- Institute of Plant and Environmental Sciences, Faculty of Agrobiology and Food Resources, Slovak University of Agriculture, Tr. A. Hlinku 2, 94976 Nitra, Slovakia
| | - Marianna Schwarzová
- Department of Fruit Science, Viticulture and Enology, Faculty of Horticulture and Landscape Engineering, Slovak University of Agriculture, Tr. A. Hlinku 2, 94976 Nitra, Slovakia
| | - Miroslava Kačániová
- Department of Fruit Science, Viticulture and Enology, Faculty of Horticulture and Landscape Engineering, Slovak University of Agriculture, Tr. A. Hlinku 2, 94976 Nitra, Slovakia
- Department of Bioenergetics, Food Analysis and Microbiology, Institute of Food Technology and Nutrition, University of Rzeszow, Cwiklinskiej 1, 35-601 Rzeszow, Poland
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Paira DA, Olivera C, Tissera AD, Molina RI, Olmedo JJ, Rivero VE, Saka HA, Motrich RD. Ureaplasma urealyticum and Mycoplasma hominis urogenital infections associate with semen inflammation and decreased sperm quality. J Leukoc Biol 2023; 113:18-26. [PMID: 36822158 DOI: 10.1093/jleuko/qiac006] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Indexed: 01/11/2023] Open
Abstract
Ureaplasma urealyticum and Mycoplasma hominis are among the most prevalent sexually transmitted infections proposed to induce urogenital inflammation and impair sperm quality. However, the topic remains controversial since contradictory findings have been reported. Herein, we performed a comprehensive analysis of U. urealyticum and M. hominis urogenital infections and their association with urogenital inflammation (i.e., leukocyte subsets and inflammatory cytokines in semen,) and sperm quality parameters in a cohort of men with couple's primary infertility undergoing initial infertility evaluation or with lower urinary tract symptoms and no infertility-related complaints. Overall, U. urealyticum and M. hominis infection was detected in 17.0% and 23.6% of patients, respectively, whereas the coinfection was detected in 3.8% of patients only. Remarkably, similar infection frequencies were found in the different patient subpopulations analyzed. Moreover, infections were associated with elevated semen levels of TNF, IL-1β, and IL-6 and/or increased counts of total leukocytes and their subsets, including CD4 and CD8 T lymphocytes and neutrophils. In addition, M. hominis infection and the coinfection with U. urealyticum were associated with impairments in sperm quality variables. Our results indicate that U. urealyticum and M. hominis male urogenital infections induce urogenital inflammation and decrease sperm quality, thus impairing male fertility potential. Screening for U. urealyticum and M. hominis infections and performing a comprehensive analysis of different leukocyte subsets and inflammatory cytokines in semen may be clinically helpful in the diagnosis and follow-up of male urogenital infection.
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Affiliation(s)
- Daniela A Paira
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre esq. Medina Allende, 5016, Córdoba, Argentina
| | - Carolina Olivera
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre esq. Medina Allende, 5016, Córdoba, Argentina
| | - Andrea D Tissera
- Laboratorio de Andrología y Reproducción (LAR), Blvd. Chacabuco 1123, 5000, Córdoba, Argentina
| | - Rosa I Molina
- Laboratorio de Andrología y Reproducción (LAR), Blvd. Chacabuco 1123, 5000, Córdoba, Argentina
| | - José J Olmedo
- Servicio de Urologia y Andrologia, Fundación Urológica Córdoba para la Docencia e Investigación Médica (FUCDIM), Bartolomé de las casas 3765, 5016, Córdoba, Argentina
| | - Virginia E Rivero
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre esq. Medina Allende, 5016, Córdoba, Argentina
| | - Héctor A Saka
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre esq. Medina Allende, 5016, Córdoba, Argentina
| | - Ruben D Motrich
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre esq. Medina Allende, 5016, Córdoba, Argentina
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Hepatitis B Virus and Cytomegalovirus Infections Disrupt Sperm Parameters in Males through Decreasing Mitochondrial Membrane Potential: A Case-control Study. Jundishapur J Microbiol 2022. [DOI: 10.5812/jjm-128539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: Infertility is a global problem that affects more than 15% of couples. The occurrence of this problem is about 50% in males. Viral infections cause infertility in men by different mechanisms. Objectives: This study is designed to evaluate the effects of hepatitis B virus (HBV) and cytomegalovirus (CMV) infection on male fertility and determine the mechanisms involved. Methods: A total of 73 males were included in the present study. They were assigned to the groups healthy fertile (n = 22 volunteers) as the healthy controls, non-infected infertile (n = 27), HBV-infected infertile (n = 14), and CMV-infected infertile (n = 10). The sperm parameters, including count, morphology, progressive motility (PR), and progressive + non-progressive motility (PR + NP), were analyzed in their semen. The semen samples of all studied participants were subjected to polymerase chain reaction to determine the presence of HBV or CMV infection. Mitochondrial membrane potential (MMP) and tumor necrosis factor-alpha (TNF-α) were also assessed. Results: Our findings showed that all sperm parameters, including count, morphology, PR, and PR + NP, decreased in males with HBV and CMV infections compared to the healthy control group (P < 0.01 in all cases). MMP declined in HBV- and CMV-infected males compared to the healthy control group (P < 0.001). Conversely, the TNF-α level of semen in HBV- and CMV-infected men was significantly higher than in the healthy control group (P < 0.001). Conclusions: The results of the present study demonstrated that HBV and CMV infections lead to male infertility through increasing TNF-α and decreasing sperm MMP.
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Tvrdá E, Ďuračka M, Benko F, Lukáč N. Bacteriospermia - A formidable player in male subfertility. Open Life Sci 2022; 17:1001-1029. [PMID: 36060647 PMCID: PMC9386612 DOI: 10.1515/biol-2022-0097] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 04/29/2022] [Accepted: 05/18/2022] [Indexed: 11/24/2022] Open
Abstract
Bacterial colonization of male reproductive tissues, cells, and fluids, and the subsequent impact of bacteria on the sperm architecture, activity, and fertilizing potential, has recently gained increased attention from the medical and scientific community. Current evidence strongly emphasizes the fact that the presence of bacteria in semen may have dire consequences on the resulting male fertility. Nevertheless, the molecular basis underlying bacteriospermia-associated suboptimal semen quality is sophisticated, multifactorial, and still needs further understanding. Bacterial adhesion and subsequent sperm agglutination and immobilization represent the most direct pathway of sperm-bacterial interactions. Furthermore, the release of bacterial toxins and leukocytic infiltration, associated with a massive outburst of reactive oxygen species, have been repeatedly associated with sperm dysfunction in bacteria-infested semen. This review serves as a summary of the present knowledge on bacteriospermia-associated male subfertility. Furthermore, we strived to outline the currently available methods for assessing bacterial profiles in semen and to outline the most promising strategies for the prevention and/or management of bacteriospermia in practice.
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Affiliation(s)
- Eva Tvrdá
- Department of Animal Physiology, Institute of Applied Biology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, Nitra-Chrenová, 949 76, Slovakia
| | - Michal Ďuračka
- Department of Animal Physiology, Institute of Applied Biology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, Nitra-Chrenová, 949 76, Slovakia
| | - Filip Benko
- Department of Animal Physiology, Institute of Applied Biology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, Nitra-Chrenová, 949 76, Slovakia
| | - Norbert Lukáč
- Department of Animal Physiology, Institute of Applied Biology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, Nitra-Chrenová, 949 76, Slovakia
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Possible Implications of Bacteriospermia on the Sperm Quality, Oxidative Characteristics, and Seminal Cytokine Network in Normozoospermic Men. Int J Mol Sci 2022; 23:ijms23158678. [PMID: 35955814 PMCID: PMC9369207 DOI: 10.3390/ijms23158678] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 07/27/2022] [Accepted: 08/02/2022] [Indexed: 02/06/2023] Open
Abstract
This study focused on the identification of bacterial profiles of semen in normozoospermic men and their possible involvement in changes to the sperm structural integrity and functional activity. Furthermore, we studied possible fluctuations of selected cytokines, oxidative markers, and antibacterial proteins as a result of bacterial presence in the ejaculate. Sperm motility was assessed with computer-assisted sperm analysis, while sperm apoptosis, necrosis and acrosome integrity were examined with fluorescent methods. Reactive oxygen species (ROS) generation was quantified via luminometry, sperm DNA fragmentation was evaluated using the TUNEL protocol and chromatin-dispersion test, while the JC-1 assay was applied to evaluate the mitochondrial membrane potential. Cytokine levels were quantified with the biochip assay, whilst selected antibacterial proteins were quantified using the ELISA method. The predominant species identified by the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were Staphylococcus hominis, Staphylococcus capitis and Micrococcus luteus. The results revealed that the sperm quality decreased proportionally to the increasing bacterial load and occurrence of conditionally pathogenic bacteria, including Enterococcus faecalis, Staphylococcus aureus and Escherichia coli. Antimicrobial susceptibility tests revealed a substantial resistance of randomly selected bacterial strains to ampicillin, vancomycin, tobramycin, and tetracycline. Furthermore, an increased bacterial quantity in semen was accompanied by elevated levels of pro-inflammatory cytokines, including interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor alpha as well as ROS overproduction and lipid peroxidation of the sperm membranes. Our results suggest that semen quality may be notably affected by the bacterial quantity as well as quality. It seems that bacteriospermia may be associated with inflammatory processes, oxidative stress, sperm structural deterioration, and a subsequent risk for the development of subfertility, even in normozoospermic males.
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19
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Vogt MB, McDonald EM, Delorey M, Mead PS, Hook SA, Hinckley AF, Werre SR, Brault AC, Duggal NK. Prolonged shedding of Zika virus in human semen is associated with male reproductive tract inflammation. J Infect Dis 2022; 226:1140-1150. [PMID: 35924442 DOI: 10.1093/infdis/jiac329] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Accepted: 08/01/2022] [Indexed: 11/13/2022] Open
Abstract
Zika virus (ZIKV) is a mosquito-borne flavivirus that causes congenital defects. Sexual transmission of ZIKV was confirmed in a recent epidemic; however, mechanisms behind ZIKV infection and persistence in the male reproductive tract are unknown. Previously, we found that ∼33% of men with symptomatic ZIKV infections shed ZIKV RNA in semen, and some men shed ZIKV RNA for >3 months. Here, we evaluated the semen of 49 ZIKV-infected men to identify immune factors correlating with long-term ZIKV shedding in semen and ZIKV-infected cell types in semen. We found prolonged ZIKV RNA shedding in semen was associated with male reproductive tract inflammation, indicated by higher leukocyte counts and inflammatory cytokine concentrations in semen of long-term versus short-term shedders. Additionally, we found ZIKV RNA in seminal leukocytes and epithelial cells. This study of human semen from ZIKV-infected men provides critical insights into impacts of ZIKV on male reproductive tract health.
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Affiliation(s)
- Megan B Vogt
- Department of Biomedical Sciences and Pathobiology Virginia-Maryland College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg Virginia 24061 United States of America
| | - Erin M McDonald
- Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Fort Collins, Colorado 80521, United States of America
| | - Mark Delorey
- Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Fort Collins, Colorado 80521, United States of America
| | - Paul S Mead
- Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Fort Collins, Colorado 80521, United States of America
| | - Sarah A Hook
- Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Fort Collins, Colorado 80521, United States of America
| | - Alison F Hinckley
- Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Fort Collins, Colorado 80521, United States of America
| | - Stephen R Werre
- Department of Population Health Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, United States of America
| | - Aaron C Brault
- Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Fort Collins, Colorado 80521, United States of America
| | - Nisha K Duggal
- Department of Biomedical Sciences and Pathobiology Virginia-Maryland College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg Virginia 24061 United States of America
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20
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Sorsa T, Nwhator SO, Sakellari D, Grigoriadis A, Umeizudike KA, Brandt E, Keskin M, Tervahartiala T, Pärnänen P, Gupta S, Mohindra R, Bostanci N, Buduneli N, Räisänen IT. aMMP-8 Oral Fluid PoC Test in Relation to Oral and Systemic Diseases. FRONTIERS IN ORAL HEALTH 2022; 3:897115. [PMID: 35757444 PMCID: PMC9226345 DOI: 10.3389/froh.2022.897115] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 05/04/2022] [Indexed: 12/24/2022] Open
Abstract
The manuscript uses the previously published literature and highlights the benefits of active-matrix metalloproteinase (aMMP)-8 chairside/point-of-care (PoC) diagnostic tools as adjunctive measures in oral and systemic diseases. Previous studies suggest that as a biomarker, aMMP-8 is more precise than total MMP-8, MMP-9, MMP-2, MMP-3, MMP-13, MMP-7, MMP-1, calprotectin, myeloperoxidase (MPO), human neutrophil elastase (HNE), tissue inhibitor of matrix metalloproteinase (TIMP)-1, and bleeding of probing (BOP). Therefore, aMMP-8 could be implemented as the needed key biomarker for the new disease classification for both periodontitis and peri-implantitis. With a sensitivity to the tune of 75-85% and specificity in the range of 80-90%, lateral flow aMMP-8 PoC testing is comparable to catalytic protease activity assays for aMMP-8. The test can be further applied to estimate the glycemic status of an individual, to ascertain whether a person is at risk for COVID-19, in managing the oral side effects of radiotherapy carried in head and neck cancers, and in selected cases pertaining to reproductive health. In the future, aMMP-8 could find application as a potential systemic biomarker in diseases affecting the cardiovascular system, cancers, bacteremia, sepsis, diabetes, obesity, meningitis, as well as pancreatitis. The aMMP-8 PoCT is the first practical test in the emerging new dental clinical field, that is, oral clinical chemistry representing oral medicine, clinical chemistry, peri-implantology, and periodontology.
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Affiliation(s)
- Timo Sorsa
- Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Section of Oral Health and Periodontology, Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Solna, Sweden
| | | | - Dimitra Sakellari
- Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Andreas Grigoriadis
- Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, Thessaloniki, Greece
- 424 General Army Hospital, Thessaloniki, Greece
| | - Kehinde Adesola Umeizudike
- Department of Preventive Dentistry, Faculty of Dental Sciences, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Ella Brandt
- Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Mutlu Keskin
- Oral and Dental Health Department, Altinbaş University, Istanbul, Turkey
| | - Taina Tervahartiala
- Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Pirjo Pärnänen
- Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Shipra Gupta
- Oral Health Sciences Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ritin Mohindra
- Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Nagihan Bostanci
- Section of Oral Health and Periodontology, Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Solna, Sweden
| | - Nurcan Buduneli
- Department of Periodontology, Faculty of Dentistry, Ege University, Izmir, Turkey
| | - Ismo Tapani Räisänen
- Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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21
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Karabulut S, Gürsoy Gürgen D, Kutlu P, Keskin İ. The Role of TNF-α and Its Target HSP-70 in Triggering Apoptosis in Normozoospermic and Non-Normozoospermic Samples. Biopreserv Biobank 2022; 20:485-492. [PMID: 35652686 DOI: 10.1089/bio.2021.0056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Objective: Semen analysis is performed as one of the screening tests for infertility, including motility, morphology, and concentration observation. We aimed to investigate the expression rates of tumor necrosis factor-α (TNF-α) and heat shock protein (HSP)-70 as two opposite affectors of apoptosis in men with normal semen parameters and abnormal parameters to find the possible effect of this pathway on sperm parameters. We also aimed to investigate the apoptotic markers (DNA fragmentation and Caspase-3 expression) to observe the correlation of this pathway with apoptosis. Materials and Methods: A total of 32 men who applied for infertility evaluation were included in the study. Semen analysis was performed according to WHO criteria. Liquefaction time, appearance, volume, pH, viscosity, sperm concentration, total motility rate, sperm motility, and percentage of spermatozoa with normal morphology were determined. TNF-α, HSP-70, and Caspase-3 immunolocalization were scored histologically. A sperm chromatin dispersion test was used to observe DNA fragmentation. Results: There was no significant difference in TNF-α protein expression rate (mild level). The HSP-70 expression rate was lower, especially in the head region of normo. Caspase-3 was higher totally in non-normo. DNA fragmentation levels were similar in both the groups. Conclusion: From TNF-α protein expression at the mild level in both the groups, it may be hypothesized that the apoptotic pathway might not be triggered by the extrinsic pathway. We found a negative correlation between HSP-70 and Caspase-3 expressions, providing further evidence that HSP-70 works as an inhibitor to apoptosis. This, particularly on specific points, made us think the communication might begin in the anterior chamber, then flow through the cell body to the tail. HSP-70 expression was lower in normo than in non-normo, indicating the possible role of HSP-70 as an answer to any type of stressor in non-normozoospermic patients. Correspondingly, it may be concluded that HSP has an antiapoptotic effect, causing inhibition in the elimination of abnormal sperm cells impairing sperm parameters.
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Affiliation(s)
- Seda Karabulut
- Department of Histology and Embryology, Istanbul Medipol University, School of Medicine, Istanbul, Turkey.,Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, Turkey
| | - Duygu Gürsoy Gürgen
- Department of Histology and Embryology, Istanbul Medipol University, School of Medicine, Istanbul, Turkey.,Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, Turkey
| | - Pelin Kutlu
- Fertility Center, Çamlıca Medicana Hospital, Istanbul, Turkey
| | - İlknur Keskin
- Department of Histology and Embryology, Istanbul Medipol University, School of Medicine, Istanbul, Turkey.,Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, Turkey
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22
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Paira DA, Silvera-Ruiz S, Tissera A, Molina RI, Olmedo JJ, Rivero VE, Motrich RD. Interferon γ, IL-17, and IL-1β impair sperm motility and viability and induce sperm apoptosis. Cytokine 2022; 152:155834. [PMID: 35217429 DOI: 10.1016/j.cyto.2022.155834] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 02/07/2022] [Accepted: 02/15/2022] [Indexed: 11/03/2022]
Abstract
Urogenital inflammation is a known cause of male infertility. Increased levels of inflammatory cytokines, leukocyte counts and oxidative stress are highly detrimental for sperm quality thus compromising male fertility. Although cytokines affect sperm by recruiting and activating leukocytes consequently inducing tissue inflammation and oxidative stress, scarce to absent data have been reported about the putative direct effects of inflammatory cytokines on spermatozoa. Herein, we analyzed whether IFNγ, IL-17A, IL-1β, and IL-8 can alter human sperm motility and viability per se. Fractions of viable and motile spermatozoa from normospermic healthy donors were in vitro incubated with recombinant human IFNγ, IL-17A, IL-1β or IL-8 and sperm ROS production, motility, viability and apoptosis were analyzed. Sperm exposed to different concentrations of IFNγ, IL-17A and IL-1β, or a combination of them, for either 1 or 3 h showed significantly increased levels of mitochondrial ROS production and reduced motility and viability with respect to sperm incubated with vehicle. Moreover, the exposure to IFNγ, IL-17A and IL-1β resulted in significantly higher levels of early and/or late apoptotic and/or necrotic spermatozoa. Interestingly, no significant differences in sperm motility, viability and apoptosis were observed in sperm incubated with the concentrations of IL-8 analyzed, for either 1 or 3 h, with respect to sperm incubated with vehicle. In conclusion, our results indicate that IFNγ, IL-17A and IL-1β per se impair sperm motility and decreases viability by triggering increased mitochondrial ROS production and inducing sperm apoptosis. Our results suggest that screening inflammatory cytokines in semen would be an additional helpful tool for the diagnostic workup of male infertility.
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Affiliation(s)
- Daniela Andrea Paira
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina
| | - Silene Silvera-Ruiz
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina
| | - Andrea Tissera
- Laboratorio de Andrología y Reproducción (LAR), Córdoba, Argentina
| | | | - José Javier Olmedo
- Fundación Urológica Córdoba para la Docencia e Investigación Médica (FUCDIM), Córdoba, Argentina
| | - Virginia Elena Rivero
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina
| | - Ruben Dario Motrich
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
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23
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Aitken RJ, Drevet JR, Moazamian A, Gharagozloo P. Male Infertility and Oxidative Stress: A Focus on the Underlying Mechanisms. Antioxidants (Basel) 2022; 11:antiox11020306. [PMID: 35204189 PMCID: PMC8868102 DOI: 10.3390/antiox11020306] [Citation(s) in RCA: 90] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 01/25/2022] [Accepted: 01/31/2022] [Indexed: 01/27/2023] Open
Abstract
Reactive oxygen species (ROS) play a critical role in defining the functional competence of human spermatozoa. When generated in moderate amounts, ROS promote sperm capacitation by facilitating cholesterol efflux from the plasma membrane, enhancing cAMP generation, inducing cytoplasmic alkalinization, increasing intracellular calcium levels, and stimulating the protein phosphorylation events that drive the attainment of a capacitated state. However, when ROS generation is excessive and/or the antioxidant defences of the reproductive system are compromised, a state of oxidative stress may be induced that disrupts the fertilizing capacity of the spermatozoa and the structural integrity of their DNA. This article focusses on the sources of ROS within this system and examines the circumstances under which the adequacy of antioxidant protection might become a limiting factor. Seminal leukocyte contamination can contribute to oxidative stress in the ejaculate while, in the germ line, the dysregulation of electron transport in the sperm mitochondria, elevated NADPH oxidase activity, or the excessive stimulation of amino acid oxidase action are all potential contributors to oxidative stress. A knowledge of the mechanisms responsible for creating such stress within the human ejaculate is essential in order to develop better antioxidant strategies that avoid the unintentional creation of its reductive counterpart.
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Affiliation(s)
- Robert John Aitken
- Priority Research Centre for Reproductive Science, Discipline of Biological Sciences, School of Environmental and Life Sciences, College of Engineering Science and Environment, University of Newcastle, Callaghan, NSW 2308, Australia
- Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia
- Correspondence: ; Tel.: +61-2-4921-6851
| | - Joël R. Drevet
- GReD Institute, INSERM U1103-CNRS UMR6293—Université Clermont Auvergne, Faculty of Medicine, CRBC Building, 28 Place Henri Dunant, 63001 Clermont-Ferrand, France; (J.R.D.); (A.M.)
| | - Aron Moazamian
- GReD Institute, INSERM U1103-CNRS UMR6293—Université Clermont Auvergne, Faculty of Medicine, CRBC Building, 28 Place Henri Dunant, 63001 Clermont-Ferrand, France; (J.R.D.); (A.M.)
- CellOxess LLC, Ewing, NJ 08628, USA;
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24
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Mahdavinezhad F, Farmani AR, Pakniat H, Taghavi S, Gharaei R, Valipour J, Amidi F. COVID-19 and varicocele: the possible overlap factors and the common therapeutic approaches. Am J Reprod Immunol 2021; 87:e13518. [PMID: 34967487 DOI: 10.1111/aji.13518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 12/02/2021] [Accepted: 12/27/2021] [Indexed: 12/15/2022] Open
Abstract
Varicocele is recognized as one of the main attributable causes of male infertility which can affect spermatogenesis by various pathophysiological mechanisms. Recent studies have identified oxidative stress and reduction in antioxidant, hyperthermia, hypoxia, hormonal dysfunction, and inflammatory conditions as major factors in the pathophysiology of varicocele, all of which have known direct associations with the coronavirus disease 2019 (COVID-19) and can significantly increase the risk of detrimental COVID-19-related outcomes. Emerging data have shown an association between COVID-19 and inflammation, overproduction of cytokine, and other pathophysiological processes. The present review, summarizes the current understanding of the pathophysiology of varicocele and investigates the potential correlation between the severity of COVID-19 and the varicocele disease. In addition, various possible treatments which can be effective in both diseases were examined. Despite numerous challenges associated with the prevalence of COVID-19 in healthcare systems in infected countries, special attention should be given to maintaining a high level of care for complex patients with a pre-existing disease such as varicocele and providing appropriate practical advice for optimal control of the COVID-19 disease. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Forough Mahdavinezhad
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Reza Farmani
- Department of Tissue Engineering, Faculty of Advanced Technologies, Tehran University of Medical Sciences, Tehran, Iran.,Tissue Engineering Department, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Hamideh Pakniat
- Department of Obstetrics and Gynecology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Saeed Taghavi
- Iran Polymer and Petrochemical Institute, Tehran, Iran
| | - Roghaye Gharaei
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Jamal Valipour
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Fardin Amidi
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Department of Infertility, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
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25
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Akthar I, Marey MA, Kim Y, Shimada M, Suarez SS, Miyamoto A. Sperm interaction with the uterine innate immune system: toll-like receptor 2 (TLR2) is a main sensor in cattle. Reprod Fertil Dev 2021; 34:139-148. [PMID: 35231265 DOI: 10.1071/rd21265] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
During the passage through the female reproductive tract, sperm interact with various compartments and their immune systems. The immune system that protects the female against pathogens also could destroy sperm or prevent them from reaching the site of fertilisation. In particular, the uterine innate immune response is crucial from the perspectives of both the sperm and the uterus. Following insemination, sperm immediately start to trigger inflammation in the uterus by entering uterine glands and activating an innate immune response. In cattle, the activation occurs mainly via TLR2 signalling, if not the only one, between sperm and the uterine epithelium lining the glands. This acute immune response is manifested as the upregulation of mRNA expression of IL8, TNFA, IL1B , and PGES . As a consequence, many sperm are trapped by polymorphonuclear neutrophils, the first and major component of innate immunity. The sperm-induced uterine innate immune responses apparently serve to clear the uterus of excess sperm and, importantly, prepare the endometrium for implantation. Pathophysiological conditions in the uterus seriously disrupt this phenomenon, and thus could directly decrease fertility.
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Affiliation(s)
- Ihshan Akthar
- Global Agromedicine Research Center (GAMRC), Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan
| | - Mohamed A Marey
- Global Agromedicine Research Center (GAMRC), Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan; and Department of Theriogenology, Faculty of Veterinary Medicine, Damanhur University, Behera, Egypt
| | - Yejin Kim
- Global Agromedicine Research Center (GAMRC), Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan
| | - Masayuki Shimada
- Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima 739-8528, Japan
| | - Susan S Suarez
- Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA
| | - Akio Miyamoto
- Global Agromedicine Research Center (GAMRC), Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan
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26
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Metin Mahmutoglu A, Hurre Dirie S, Hekim N, Gunes S, Asci R, Henkel R. Polymorphisms of androgens-related genes and idiopathic male infertility in Turkish men. Andrologia 2021; 54:e14270. [PMID: 34632603 DOI: 10.1111/and.14270] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Accepted: 09/24/2021] [Indexed: 01/01/2023] Open
Abstract
Androgens, testosterone and dihydrotestosterone (DHT) are endocrine regulators of spermatogenesis and act via androgen receptor (AR). The aim of this study was to investigate the association(s) of AR (CAG repeat length), SRD5A2 (rs523349, V89L) and TNF-α (rs1800629, -308G/A) polymorphisms with idiopathic male infertility in Turkish men. This case-control study consisted of 312 men with idiopathic infertility and 113 fertile men. Polyacrylamide gel electrophoresis (PAGE) or PCR-restriction fragment length polymorphism methods were used for genotyping. The mean AR CAG repeat length was significantly longer in infertile men than in fertile men (p = 0.015). However, there was no significant association between the SRD5A2 genotypes (VV, VL and LL) and the risk of infertility (p = 0.516). The genotype frequency and allele distribution of TNF-α -308G/A polymorphism (GG, GA, AA genotypes and G, A alleles) were not associated with male infertility (p = 0.779 and p = 0.743 respectively). AR CAG repeat expansion might be one of the risk factors for idiopathic male infertility in Turkish men. Further studies investigating the association of male infertility with AR CAG, V89L and -308G/A polymorphisms are warranted to understand the possible associations among them.
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Affiliation(s)
- Asli Metin Mahmutoglu
- Faculty of Medicine, Department of Medical Biology, Ondokuz Mayis University, Samsun, Turkey
| | - Saadiq Hurre Dirie
- Faculty of Medicine, Department of Medical Biology, Ondokuz Mayis University, Samsun, Turkey
| | - Neslihan Hekim
- Faculty of Medicine, Department of Medical Biology, Ondokuz Mayis University, Samsun, Turkey
| | - Sezgin Gunes
- Faculty of Medicine, Department of Medical Biology, Ondokuz Mayis University, Samsun, Turkey.,Health Sciences Institute, Department of Multidisciplinary Molecular Medicine, Ondokuz Mayis University, Samsun, Turkey
| | - Ramazan Asci
- Health Sciences Institute, Department of Multidisciplinary Molecular Medicine, Ondokuz Mayis University, Samsun, Turkey.,Faculty of Medicine, Department of Urology, Ondokuz Mayis University, Samsun, Turkey
| | - Ralf Henkel
- Department of Medical Bioscience, University of the Western Cape, Bellville, South Africa.,American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, Ohio, USA.,Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
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27
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du Fossé NA, Lashley EELO, van Beelen E, Meuleman T, le Cessie S, van Lith JMM, Eikmans M, van der Hoorn MLP. Identification of distinct seminal plasma cytokine profiles associated with male age and lifestyle characteristics in unexplained recurrent pregnancy loss. J Reprod Immunol 2021; 147:103349. [PMID: 34246867 DOI: 10.1016/j.jri.2021.103349] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 05/09/2021] [Accepted: 07/01/2021] [Indexed: 11/19/2022]
Abstract
BACKGROUND Seminal plasma contains a wide range of cytokines, chemokines and growth factors. Part of these signalling molecules assist in inducing a state of active maternal immune tolerance towards the fetus. Disbalances in seminal plasma content may contribute to pregnancy loss. This study investigated cytokine expression profiles in seminal plasma of male partners of couples with unexplained recurrent pregnancy loss (RPL) and the association with clinical and lifestyle characteristics, including smoking, alcohol consumption and body mass index (BMI). METHODS In the seminal plasma of 52 men who visited a specialised RPL clinic the levels of 25 pre-selected cytokines, chemokines and growth factors were measured by Bio-Plex assay or ELISA. Two-way hierarchical cluster analysis was performed. Identified patient clusters were compared on clinical and lifestyle characteristics. RESULTS Two distinct cytokine expression profiles in the seminal plasma were revealed by cluster analysis. Patient cluster I showed relatively higher levels of pro-inflammatory cytokines, including IL-1α, IL-1β, IL-6, IL-8, IL-12, IL-18 and TNF-α, compared to Patient cluster II. Men belonging to Patient cluster I were significantly older and had significantly more lifestyle risk factors compared to men in Patient cluster II. CONCLUSION Cluster analysis suggested the existence of a less favourable pro-inflammatory cytokine expression profile, being present in part of men affected by RPL and associated with advanced male age and lifestyle risk factors. These findings may serve as a starting point for further research into underlying mechanisms and ultimately lead to novel diagnostic and therapeutic approaches for couples with RPL.
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Affiliation(s)
- N A du Fossé
- Department of Gynaecology and Obstetrics, Leiden University Medical Center, Leiden, the Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
| | - E E L O Lashley
- Department of Gynaecology and Obstetrics, Leiden University Medical Center, Leiden, the Netherlands
| | - E van Beelen
- Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands
| | - T Meuleman
- Department of Gynaecology and Obstetrics, Leiden University Medical Center, Leiden, the Netherlands
| | - S le Cessie
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands
| | - J M M van Lith
- Department of Gynaecology and Obstetrics, Leiden University Medical Center, Leiden, the Netherlands
| | - M Eikmans
- Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands
| | - M L P van der Hoorn
- Department of Gynaecology and Obstetrics, Leiden University Medical Center, Leiden, the Netherlands
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28
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Liu KS, Mao XD, Pan F, An RF. Effect and mechanisms of reproductive tract infection on oxidative stress parameters, sperm DNA fragmentation, and semen quality in infertile males. Reprod Biol Endocrinol 2021; 19:97. [PMID: 34183027 PMCID: PMC8237428 DOI: 10.1186/s12958-021-00781-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 06/10/2021] [Indexed: 11/24/2022] Open
Abstract
Recent years have seen a rising incidence of male infertility, mostly caused by the decline of sperm quality. The ratio of infertile males to infertile females has escalated from 3:7 in 2013 to current 5:5, which turns male infertility into the research focus of reproductive medicine. This study aimed to clarify the effect of reproductive tract infection by ureaplasma urealyticum (UU) and chlamydia trachomatis (CT) on the DNA integrity and routine semen parameters of infertile males. A retrospective study was performed. A total of 259 infertile males who were treated at the Andrological Laboratory Examination and Reproductive Medicine Center in our hospital were analyzed. qRT-PCR was used to examine the infection status of CT and UU. According to the eligibility criteria, we evaluated the semen parameters and biochemical data of 253 men. Based on the results of PCR, the subjects were divided into four groups: Group I (CT positive, 63 cases), Group II (UU positive, 60 cases), Group III (CT positive and UU positive, 62 cases), and Group IV (no infection, 68 cases). DNA fragmentation index (DFI), sperm count, vitality and morphology, elastase level, seminal plasma malondialdehyde (MDA), and total antioxidant capacity (TAC) were assessed. Compared to Group IV, three groups (Group I, Group II and Group III) showed difference in semen volume, proportion of sperm with normal morphology, sperm motility, progressive motility, and vitality (P < 0.05). Compared to Group IV, Group II and Group III showed difference in DFI (P < 0.05). Compared to Group IV, Group II and Group III showed difference in elastase level (P < 0.05). VCL, VSL, VAP, WOB, ROS, TM, HDS showed differences between groups of abnormal/normal WBC (*P < 0.01).UU infection significantly increased the level of seminal leukocytes only in Group II, but not in the other three groups, indicating that UU is a factor to increase the level of seminal leukocytes. Compared with the normal leukocyte group, there were significant differences in total motility, forward motility and normal sperm ratio between the two groups. The proportion of sperm with abnormal morphology (mostly in the head) showed obvious difference between groups of high and normal seminal leukocytic levels. At the same time, in this study, SCGE and SCD verified that leukocytes could damage sperm DNA by increasing ROS, which ultimately affects male fertility.
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Affiliation(s)
- Kang-Sheng Liu
- grid.452438.cDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shannxi 710061 China
- grid.459791.70000 0004 1757 7869Department of Clinical Laboratory, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, 210029 Jiangsu China
| | - Xiao-Dong Mao
- grid.410745.30000 0004 1765 1045Department of Endocrinology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028 Jiangsu China
| | - Feng Pan
- grid.459791.70000 0004 1757 7869Department of Andrology, State Key Laboratory of Reproductive Medicine, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, 210029 Jiangsu China
| | - Rui Fang An
- grid.452438.cDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shannxi 710061 China
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Chen Y, Bi F, Sun Z. A network pharmacology approach to determine the underlying mechanisms of action of Yishen Tongluo formula for the treatment of oligoasthenozoospermia. PLoS One 2021; 16:e0252906. [PMID: 34153045 PMCID: PMC8216565 DOI: 10.1371/journal.pone.0252906] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 05/22/2021] [Indexed: 12/15/2022] Open
Abstract
Oligoasthenozoospermia is a complex disease caused by a variety of factors, and its incidence is increasing yearly worldwide. Yishen Tongluo formula (YSTLF), created by Professor Sun Zixue, has been used to treat oligoasthenozoospermia in clinical practice for several decades with a good therapeutic effect. However, the chemical and pharmacological profiles of YSTLF remain unclear and need to be elucidated. In this study, a network pharmacology approach was applied to explore the potential mechanisms of YSTLF in oligoasthenozoospermia treatment. All of the compounds in YSTLF were retrieved from the corresponding databases, and the bioactive ingredients were screened according to their oral bioavailability (OB) and drug-likeness (DL). The potential proteins of YSTLF were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) database, while the potential genes of oligoasthenozoospermia were obtained from the GeneCards database and the DisGeNET database. The STRING database was used to construct an interaction network according to the common targets identified by the online tool Venny for YSTLF and oligoasthenozoospermia. The topological characteristics of nodes were visualized and analyzed through Cytoscape. Biological functions and significant pathways were determined and analyzed using the Gene Ontology (GO) knowledgebase, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Metascape. Finally, the disease-formula-compound-target-pathway network was constructed by Cytoscape. A total of 106 bioactive ingredients and 134 potential targets from YSTLF were associated with oligoasthenozoospermia or considered to be therapeutically relevant. Pathway analysis indicated that the PI3K/Akt, MAPK and apoptosis signaling pathways were significant pathways involved in oligoasthenozoospermia. In conclusion, the current study expounded the pharmacological actions and molecular mechanisms of YSTLF in treating oligoasthenozoospermia from a holistic viewpoint. The potential molecular mechanisms were closely related to antioxidative stress, antiapoptosis and anti-inflammation, with TNF, CCND1, ESR1, NFKBIA, NR3C1, MAPK8, and IL6 being possible targets. This network pharmacology prediction may offer a helpful tool to illustrate the molecular mechanisms of the Chinese herbal compound YSTLF in oligoasthenozoospermia treatment.
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Affiliation(s)
- Yangdi Chen
- Henan University of Chinese Medicine, Zhengzhou, Henan, P. R. China
| | - Fanggang Bi
- Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China
| | - Zixue Sun
- Department of Reproductive Medicine, Henan Province Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Chinese Medicine), Zhengzhou, Henan, P. R. China
- * E-mail:
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Microbiological Evaluation and Sperm DNA Fragmentation in Semen Samples of Patients Undergoing Fertility Investigation. Genes (Basel) 2021; 12:genes12050654. [PMID: 33925640 PMCID: PMC8145398 DOI: 10.3390/genes12050654] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 04/19/2021] [Accepted: 04/26/2021] [Indexed: 12/13/2022] Open
Abstract
Fifteen percent of male infertility is associated with urogenital infections; several pathogens are able to alter the testicular and accessory glands' microenvironment, resulting in the impairment of biofunctional sperm parameters. The purpose of this study was to assess the influence of urogenital infections on the quality of 53 human semen samples through standard analysis, microbiological evaluation, and molecular characterization of sperm DNA damage. The results showed a significant correlation between infected status and semen volume, sperm concentration, and motility. Moreover, a high risk of fragmented sperm DNA was demonstrated in the altered semen samples. Urogenital infections are often asymptomatic and thus an in-depth evaluation of the seminal sample can allow for both the diagnosis and therapy of infections while providing more indicators for male infertility management.
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Heydari H, Ghiasi R, Ghaderpour S, Keyhanmanesh R. The Mechanisms Involved in Obesity-Induced Male Infertility. Curr Diabetes Rev 2021; 17:259-267. [PMID: 32814535 DOI: 10.2174/1573399816666200819114032] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 07/20/2020] [Accepted: 07/29/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Obesity resulted by imbalance between the intake of energy and energy consumption can lead to growth and metabolic disease development in people. Both in obese men and animal models, several studies indicate that obesity leads to male infertility. OBJECTIVE This review has discussed some mechanisms involved in obesity-induced male infertility. METHODS Online documents were searched through Science Direct, Pubmed, Scopus, and Google Scholar websites dating from 1959 to recognize studies on obesity, kisspeptin, leptin, and infertility. RESULTS Obesity induced elevated inflammatory cytokines and oxidative stress can affect male reproductive functions, including spermatogenesis disorders, reduced male fertility power and hormones involved in the hypothalamus-pituitary-gonadal axis. CONCLUSION There is significant evidence that obesity resulted in male infertility. Obesity has a negative effect on male reproductive function via several mechanisms such as inflammation and oxidative stress.
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Affiliation(s)
- Hamed Heydari
- Department of Physiology, Tabriz Faculty of Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Rafighe Ghiasi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saber Ghaderpour
- Department of Physiology, Tabriz Faculty of Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Rana Keyhanmanesh
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Ajayi A, Akhigbe R. In vivo exposure to codeine induces reproductive toxicity: role of HER2 and p53/Bcl-2 signaling pathway. Heliyon 2020; 6:e05589. [PMID: 33294712 PMCID: PMC7695972 DOI: 10.1016/j.heliyon.2020.e05589] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Revised: 10/17/2020] [Accepted: 11/19/2020] [Indexed: 02/08/2023] Open
Abstract
Several studies have implicated codeine use in the aetiopathogenesis of male infertility. The purpose of this study was to investigate the role of HER2, Ki67, oestrogen and p53/Bcl-2 signaling pathways and the possible outcome of codeine cessation on codeine-induced reproductive toxicity. Thirty adult male Wistar rats of comparable ages and weights were randomly allocated into 5 groups. The control animals received distilled water per os (p.o), while animals in the low-dose (LDC) and high dose (HDC) codeine-treated groups received 2 and 5 mg/kg/day of codeine respectively p.o for 6 weeks. The animals in the low-dose codeine recovery (LDC-R) and high-dose codeine recovery (HDC-R) groups received treatment as LDC and HDC respectively followed by another drug-free six weeks, recovery period. Cessation of codeine exposure led to a partial reversal of codeine-induced poor sperm quality, reduced litter size and weight, increased oxidative testicular injury, testicular apoptosis, and testicular DNA damage caused by codeine administration. Codeine-induced gonado-spermotoxicity was associated with a reduction of circulatory testosterone, suppression of testicular HER2, Ki67, and Bcl-2 expression, down-regulation of oestrogen signaling, and upregulation of testicular caspase 3 activities and p53 signaling pathway. Conclusion: Upregulation of oestrogen signaling associated with enhanced testicular HER2 and Ki67 expression during the recovery period is seemingly beneficial in protecting against codeine-related testicular injury and infertility.
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Affiliation(s)
- A.F. Ajayi
- Department of Physiology, College of Medicine, Ladoke Akintola University of Technology, Ogbomoso, Oyo, Nigeria
| | - R.E. Akhigbe
- Department of Physiology, College of Medicine, Ladoke Akintola University of Technology, Ogbomoso, Oyo, Nigeria
- Reproductive Biology and Toxicology Research Laboratories, Oasis of Grace Hospital, Osogbo, Osun, Nigeria
- Department of Chemical Sciences, Kings University, Odeomu, Osun, Nigeria
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Li X, Ni M, Xing S, Yu Y, Zhou Y, Yang S, Li H, Zhu R, Han M. Reactive Oxygen Species Secreted by Leukocytes in Semen Induce Self-Expression of Interleukin-6 and Affect Sperm Quality. Am J Mens Health 2020; 14:1557988320970053. [PMID: 33131385 PMCID: PMC7607761 DOI: 10.1177/1557988320970053] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Reproductive tract inflammation is considered an important cause of male infertility. Increased leukocytes in semen can produce many reactive oxygen species (ROS), which affect sperm function. The aim of this study is to identify the main source of ROS in seminal plasma and to assess the effect of ROS on leukocytes. Semen samples (n = 20) with leukocyte concentration >1 × 106 were collected from a male infertility clinic. This study mainly compares the sperm function parameters of the normal group and the semen white blood cell group >1 × 106. The results identified that ROS in semen was closely related to sperm function parameters, and CD45+ leucocytes were the main source of ROS. Compared with the control group, the concentration of IL-2, IL-4, IL-6, IFN-γ, and TNF-α was higher in the experimental group. Leukocytes in semen may regulate the secretion of ROS through the mammalian target of rapamycin (mTOR) pathway. A considerable amount of ROS can upregulate the expression of IL-6 in leukocytes via the nuclear factor kappa-B (NF-kB) pathway.
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Affiliation(s)
- Xiaoping Li
- Center for Reproduction and Genetics, The First Affiliated Hospital of Soochow University, SuZhou, Jiangsu, China.,Biomedical Research Institute, Soochow University, SuZhou, Jiangsu, China
| | - Mengxia Ni
- Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, SuZhou, Jiangsu, China
| | - Shiyu Xing
- Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, SuZhou, Jiangsu, China
| | - Yi Yu
- Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, SuZhou, Jiangsu, China
| | - Yan Zhou
- Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, SuZhou, Jiangsu, China
| | - Shenmin Yang
- Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, SuZhou, Jiangsu, China
| | - Hong Li
- Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, SuZhou, Jiangsu, China
| | - Rui Zhu
- Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, SuZhou, Jiangsu, China
| | - Mutian Han
- Department of Immunology, Anhui Medical University, HeFei, China.,Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, SuZhou, Jiangsu, China
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Cacciapuoti S, Scala E, Megna M, Gallo L, Fontanella G, Ruggiero A, Savastano S, Fabbrocini G. Impact of current antipsoriatic systemic treatments on male and female fertility: what endocrinologists need to know. Minerva Endocrinol (Torino) 2020; 46:350-362. [PMID: 32720503 DOI: 10.23736/s2724-6507.20.03236-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Fertility is a function of the body that is often overlooked as a site for the expression of the side effects of certain drugs. With the approval of new drugs with a totally innovative mechanism of action, the risk assessment on fertility both in male and female is more difficult. This is particularly true in psoriasis, an invalidating inflammatory skin disease. The estimated prevalence of psoriasis in adults ranged from 0.51% to 11.43%, and in children from 0% to 1.37%, with frequent diagnosis in young patients of childbearing age. With the increasing use of new, predominantly immunosuppressive or biologic drugs for psoriasis, questions frequently arise in clinical practice as to their safety in men and women wishing to procreate. Both psoriatic patients and their physicians are concerned about adverse effects of the disease and its treatment on their future fertility, causing additional concerns in the therapeutic management of these patients. Among antipsoriatic drugs, conventional therapies are mainly involved in the onset of infertility in both sexes, exerting in some cases toxic effects against reproductive organs. Conversely, biologic agents appear to improve male and female fertility especially when gonadal impairment is related to inflammatory phenomena. There is a lack of review articles of commonly used medications in psoriasis with respect to their potential effects on fertility. The aim of this paper was to provide a practical guide for both dermatologist and endocrinologist in therapeutic management of psoriatic patients of childbearing age, considering the impact of prescribed drugs on their current and future fertility.
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Affiliation(s)
- Sara Cacciapuoti
- Section of Dermatology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy -
| | - Emanuele Scala
- Section of Dermatology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Matteo Megna
- Section of Dermatology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Lucia Gallo
- Section of Dermatology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Giuseppina Fontanella
- Section of Dermatology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Angelo Ruggiero
- Section of Dermatology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Silvia Savastano
- Unit of Endocrinology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Gabriella Fabbrocini
- Section of Dermatology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
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van Son M, Tremoen NH, Gaustad AH, Våge DI, Zeremichael TT, Myromslien FD, Grindflek E. Transcriptome profiling of porcine testis tissue reveals genes related to sperm hyperactive motility. BMC Vet Res 2020; 16:161. [PMID: 32456687 PMCID: PMC7249385 DOI: 10.1186/s12917-020-02373-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 05/13/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Sperm hyperactive motility has previously been shown to influence litter size in pigs, but little is known about the underlying biological mechanisms. The aim of this study was to use RNA sequencing to investigate gene expression differences in testis tissue from Landrace and Duroc boars with high and low levels of sperm hyperactive motility. Boars with divergent phenotypes were selected based on their sperm hyperactivity values at the day of ejaculation (day 0) (contrasts (i) and (ii) for Landrace and Duroc, respectively) and on their change in hyperactivity between day 0 and after 96 h liquid storage at 18 °C (contrast (iii)). RESULTS RNA sequencing was used to measure gene expression in testis. In Landrace boars, 3219 genes were differentially expressed for contrast (i), whereas 102 genes were differentially expressed for contrast (iii). Forty-one differentially expressed genes were identified in both contrasts, suggesting a functional role of these genes in hyperactivity regardless of storage. Zinc finger DNLZ was the most up-regulated gene in contrasts (i) and (iii), whereas the most significant differentially expressed gene for the two contrasts were ADP ribosylation factor ARFGAP1 and solute carrier SLC40A1, respectively. For Duroc (contrast (ii)), the clustering of boars based on their gene expression data did not reflect their difference in sperm hyperactivity phenotypes. No results were therefore obtained for this breed. A case-control analysis of variants identified in the Landrace RNA sequencing data showed that SNPs in NEU3, CHRDL2 and HMCN1 might be important for sperm hyperactivity. CONCLUSIONS Differentially expressed genes were identified in Landrace boars with high and low levels of sperm hyperactivity at the day of ejaculate collection and high and low change in hyperactivity after 96 h of sperm storage. The results point towards important candidate genes, biochemical pathways and sequence variants underlying sperm hyperactivity in pigs.
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Affiliation(s)
| | - Nina Hårdnes Tremoen
- Department of Biotechnology, Inland Norway University of Applied Sciences, 2318 Hamar, Norway
- Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Faculty of Biosciences, Norwegian University of Life Sciences, 1432 Ås, Norway
| | - Ann Helen Gaustad
- Norsvin SA, 2317 Hamar, Norway
- Department of Biotechnology, Inland Norway University of Applied Sciences, 2318 Hamar, Norway
| | - Dag Inge Våge
- Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Faculty of Biosciences, Norwegian University of Life Sciences, 1432 Ås, Norway
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Uyaroglu OA, Seyhoglu E, Erden A, Kilic L, Karadag O, Akdogan A, Bilgen SA, Ertenli AI, Kiraz S, Kalyoncu U. Pregnancy outcomes in partners of male ankylosing spondylitis patients treated with anti-tumour necrosis factor-α biologics: real-life results from a single-centre cross-sectional study. Rheumatol Int 2020; 40:1501-1507. [PMID: 31993731 DOI: 10.1007/s00296-020-04518-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Accepted: 01/16/2020] [Indexed: 10/25/2022]
Abstract
Most patients with inflammatory arthritis are at their reproductive ages. Use of anti-tumour necrosis factor alpha (anti-TNF-α) agents, one of the important treatment options for inflammatory arthritis, can cause foetal morbidity and mortality. While most studies on the effects of anti-TNF-α agents on pregnancy outcomes are about maternal exposure, the number of studies on the risks related to paternal exposure is insufficient. This study aimed to assess pregnancy periods and outcomes of the partners of male ankylosing spondylitis (AS) patients receiving anti-TNF-α treatment during the preconception period. Totally, 163 male AS patients using anti-TNF-α agents were identified from the Hacettepe University Biological Registry. Of these patients, 45 (27.6%) who declared that their partners got pregnant after initiation on anti-TNF-α agents were included. Data regarding demographics and drug exposure and pregnancy and infant outcomes were evaluated. Of 45 pregnancies, 39 (86.7%) resulted in healthy live births, 3 (6.7%) resulted in spontaneous abortion, and 3 (6.7%) were terminated with curettage. Of 39 live births, 34 (87.2%) were term and 5 (12.8%) were preterm, 30 (76.9%) had normal birth weight, 6 (15.4%) had low birth weight, and 3 (7.7%) had fetal macrosomia. No congenital malformations related to paternal exposure were observed. This study is valuable as being one of the studies providing pregnancy outcomes of partners of male AS patients receiving anti-TNF-α agents with its relatively high number of patients. The results suggested that paternal exposure to anti-TNF-α agents during preconception period could be safe on pregnancy outcomes.
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Affiliation(s)
- Oguz Abdullah Uyaroglu
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Sihhiye, 06100, Ankara, Turkey.
| | - Emrah Seyhoglu
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Sihhiye, 06100, Ankara, Turkey
| | - Abdulsamet Erden
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Levent Kilic
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Omer Karadag
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Ali Akdogan
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Sule Apras Bilgen
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Ali Ihsan Ertenli
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Sedat Kiraz
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Umut Kalyoncu
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
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Wang W, Liang K, Chang Y, Ran M, Zhang Y, Ali MA, Dai D, Qazi IH, Zhang M, Zhou G, Yang J, Angel C, Zeng C. miR-26a is Involved in Glycometabolism and Affects Boar Sperm Viability by Targeting PDHX. Cells 2020; 9:E146. [PMID: 31936222 PMCID: PMC7016825 DOI: 10.3390/cells9010146] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 12/26/2019] [Accepted: 12/27/2019] [Indexed: 02/06/2023] Open
Abstract
miR-26a is associated with sperm metabolism and can affect sperm motility and apoptosis. However, how miR-26a affects sperm motility remains largely unknown. Our previous study indicated that the PDHX gene is predicted to be a potential target of miR-26a, which is responsible for pyruvate oxidative decarboxylation which is considered as a key step for connecting glycolysis with oxidative phosphorylation. In this study, we first reported a potential relationship between miR-26a and PDHX and their expressions in fresh, frozen-thawed, and epididymal boar sperm. Then, sperm viability and survival were determined after transfection of miR-26a. mRNA and protein expression level of PDHX in the liquid-preserved boar sperm after transfection were also determined by RT-qPCR and Western Blot (WB). Our results showed that expression level of PDHX was significantly increased during sperm transit from epididymal caput to corpus and cauda. Similarly, expression of PDHX was significantly higher (P < 0.05) in fresh sperm as compared to epididymal cauda and frozen-thawed sperm. However, the expression of miR-26a in epididymal corpus sperm was significantly higher (P < 0.05) than that of caput and cauda sperm. Furthermore, after transfection of boar sperm with miR-26a mimic and inhibitor under liquid storage, the lowest and highest sperm viability was observed in miR-26a mimic and inhibitor treatment (P < 0.05), respectively. The protein levels of PDHX, after 24 and 48 h of transfection of miR-26a mimics and inhibitor, were notably decreased and increased (P < 0.05), respectively, as compared to negative control (NC) group. In conclusion, the novel and enticing findings of our study provide a reasonable evidence that miR-26a via PDHX, a link between glycolysis and oxidative phosphorylation, could regulate the glycometabolic pathway which eventually affect boar sperm viability and survival.
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Affiliation(s)
- Wencan Wang
- College of Animal Sciences and Technology, and Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (W.W.); (K.L.); (Y.C.); (M.R.); (Y.Z.); (M.A.A.); (D.D.); (I.H.Q.); (M.Z.); (G.Z.); (J.Y.)
| | - Kai Liang
- College of Animal Sciences and Technology, and Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (W.W.); (K.L.); (Y.C.); (M.R.); (Y.Z.); (M.A.A.); (D.D.); (I.H.Q.); (M.Z.); (G.Z.); (J.Y.)
| | - Yu Chang
- College of Animal Sciences and Technology, and Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (W.W.); (K.L.); (Y.C.); (M.R.); (Y.Z.); (M.A.A.); (D.D.); (I.H.Q.); (M.Z.); (G.Z.); (J.Y.)
| | - Mingxia Ran
- College of Animal Sciences and Technology, and Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (W.W.); (K.L.); (Y.C.); (M.R.); (Y.Z.); (M.A.A.); (D.D.); (I.H.Q.); (M.Z.); (G.Z.); (J.Y.)
| | - Yan Zhang
- College of Animal Sciences and Technology, and Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (W.W.); (K.L.); (Y.C.); (M.R.); (Y.Z.); (M.A.A.); (D.D.); (I.H.Q.); (M.Z.); (G.Z.); (J.Y.)
| | - Malik Ahsan Ali
- College of Animal Sciences and Technology, and Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (W.W.); (K.L.); (Y.C.); (M.R.); (Y.Z.); (M.A.A.); (D.D.); (I.H.Q.); (M.Z.); (G.Z.); (J.Y.)
- Department of Theriogenology, Riphah College of Veterinary Sciences, Lahore 54000, Pakistan
| | - Dinghui Dai
- College of Animal Sciences and Technology, and Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (W.W.); (K.L.); (Y.C.); (M.R.); (Y.Z.); (M.A.A.); (D.D.); (I.H.Q.); (M.Z.); (G.Z.); (J.Y.)
| | - Izhar Hyder Qazi
- College of Animal Sciences and Technology, and Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (W.W.); (K.L.); (Y.C.); (M.R.); (Y.Z.); (M.A.A.); (D.D.); (I.H.Q.); (M.Z.); (G.Z.); (J.Y.)
- Department of Veterinary Anatomy & Histology, Shaheed Benazir Bhutto University of Veterinary and Animal Sciences, Sakrand 67210, Pakistan
| | - Ming Zhang
- College of Animal Sciences and Technology, and Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (W.W.); (K.L.); (Y.C.); (M.R.); (Y.Z.); (M.A.A.); (D.D.); (I.H.Q.); (M.Z.); (G.Z.); (J.Y.)
| | - Guangbin Zhou
- College of Animal Sciences and Technology, and Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (W.W.); (K.L.); (Y.C.); (M.R.); (Y.Z.); (M.A.A.); (D.D.); (I.H.Q.); (M.Z.); (G.Z.); (J.Y.)
| | - Jiandong Yang
- College of Animal Sciences and Technology, and Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (W.W.); (K.L.); (Y.C.); (M.R.); (Y.Z.); (M.A.A.); (D.D.); (I.H.Q.); (M.Z.); (G.Z.); (J.Y.)
| | - Christiana Angel
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China;
- Department of Veterinary Parasitology, Faculty of Veterinary Sciences, Shaheed Benazir Bhutto University of Veterinary and Animal Sciences, Sakrand 67210, Pakistan
| | - Changjun Zeng
- College of Animal Sciences and Technology, and Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (W.W.); (K.L.); (Y.C.); (M.R.); (Y.Z.); (M.A.A.); (D.D.); (I.H.Q.); (M.Z.); (G.Z.); (J.Y.)
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Schulz M, Zambrano F, Schuppe HC, Wagenlehner F, Taubert A, Gaertner U, Sánchez R, Hermosilla C. Monocyte-derived extracellular trap (MET) formation induces aggregation and affects motility of human spermatozoa in vitro. Syst Biol Reprod Med 2019; 65:357-366. [PMID: 31208212 DOI: 10.1080/19396368.2019.1624873] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The presence of bacteria and/or leukocytes can alter semen quality resulting in low sperm quality and infertility. Inflammation or infection increases the numbers of PMN or macrophages/monocytes in male genital tract. Release of extracellular traps (ETs) by leukocytes has been recognized as a novel mechanism of early host innate immunity, in response to invasive pathogens. This is the first work that evaluated the mechanism of triggered ETs in monocytes co-incubated with spermatozoa or bacteria and the effect on sperm function. Selected spermatozoa and human monocytes isolated from peripheral blood were obtained by healthy donors. Two experimental models were developed, one aseptic (non-infectious) incubating spermatozoa and monocytes, and septic models (infectious) incubating spermatozoa with monocytes and uropathogenic Escherichia coli (E. coli). ETs of monocytes (METs) (DNA, global histone and citrullinated histones) were visualized by scanning electron microscopy (SEM) and immunofluorescence analyses. Progressive motility was performed at 0, 10, 30, 60, and 180 min after co-incubation with CASA system. SEM- and immunofluorescence-analyses revealed human spermatozoa alone or in the presence of E. coli as strong inducers METs. In aseptic model, the motility decreased to 65.2 ± 3.5% at 10 min of incubation and 29.3 ± 3.3% at 30 min (p < 0.001). In septic model, motility decreased to 44.5 ± 5.9% (10 min) and 12.7 ± 2.2% (30 min) (p < 0.001). MET-derived small spermatozoa aggregations were observed in both models. METs might physically block spermatozoa and decrease motility after a brief contact. This may impair male fertility, especially in patients with genital tract infections or chronic inflammation. Abbreviations: PMN: polymorphonuclear; ETs: extracellular traps; E. coli: Escherichia coli; METs: ETs of monocytes; SEM: scanning electron microscopy; NE: neutrophil elastase; MPO: myeloperoxidase; MAGI: male accessory gland infection; PBMC: peripheral blood mononuclear cells; RT: room temperature; CFU: colony forming units; CASA: computer-aided sperm analysis; H4Cit3: histone H4 citrullinated 3.
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Affiliation(s)
- Mabel Schulz
- Laboratory of Reproductive Medicine and Molecular Endocrinology, Center for Translational Medicine (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera , Temuco , Chile.,Doctoral Program in Morphological Sciences, Faculty of Medicine, Universidad de La Frontera , Temuco , Chile.,Institute of Parasitology, Biomedical Research Center Seltersberg (BFS), Justus Liebig University Giessen , Giessen , Germany
| | - Fabiola Zambrano
- Laboratory of Reproductive Medicine and Molecular Endocrinology, Center for Translational Medicine (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera , Temuco , Chile.,Department of Preclinical Science, Faculty of Medicine, Universidad de La Frontera , Temuco , Chile
| | - Hans-Christian Schuppe
- Department of Urology, Pediatric Urology and Andrology, Justus Liebig University Giessen , Giessen , Germany
| | - Florian Wagenlehner
- Department of Urology, Pediatric Urology and Andrology, Justus Liebig University Giessen , Giessen , Germany
| | - Anja Taubert
- Institute of Parasitology, Biomedical Research Center Seltersberg (BFS), Justus Liebig University Giessen , Giessen , Germany
| | - Ulrich Gaertner
- Institute of Anatomy and Cell Biology, Justus Liebig University Giessen , Giessen , Germany
| | - Rául Sánchez
- Laboratory of Reproductive Medicine and Molecular Endocrinology, Center for Translational Medicine (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera , Temuco , Chile.,Department of Preclinical Science, Faculty of Medicine, Universidad de La Frontera , Temuco , Chile
| | - Carlos Hermosilla
- Institute of Parasitology, Biomedical Research Center Seltersberg (BFS), Justus Liebig University Giessen , Giessen , Germany
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Avellar MCW, Ribeiro CM, Dias-da-Silva MR, Silva EJR. In search of new paradigms for epididymal health and disease: innate immunity, inflammatory mediators, and steroid hormones. Andrology 2019; 7:690-702. [PMID: 31207127 DOI: 10.1111/andr.12654] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 04/22/2019] [Accepted: 04/29/2019] [Indexed: 02/07/2023]
Abstract
The primary job of the epididymis is to mature and protect the luminally transiting spermatozoa. Mounting evidence is showing that innate immune components [including Toll-like receptors (TLRs) and antimicrobial proteins, among which are β-defensins] and inflammatory mediators, under the primary influence of androgens, participate in the cellular and molecular processes that define this tissue. Here, we present an overview of the contributions of these signaling pathway components during epididymal homeostasis and discuss the hypotheses as to their involvement in epididymitis, the most common urological inflammatory condition in men, frequently impairing their fertility. Drawing primarily from rodent models, we also focus on how the distribution and functional expression of innate immune components are differentially regulated in the prenatal developing epididymis, providing new insights into the disruption of these signaling pathways throughout the lifespan. Male infertility is caused by a variety of conditions, such as congenital malformations, genetic and endocrine disorders, exposure to environmental toxicants, and inflammatory/infectious conditions. More than one-third of infertile men with an idiopathic condition cannot currently be adequately diagnosed. Thinking about the innate immunity and inflammation context of the epididymis may provide new insights and directions as to how these systems contribute to male fertility, as well as also uncover urological and andrological outcomes that may aid clinicians in diagnosing and preventing epididymal pathologies.
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Affiliation(s)
- M C W Avellar
- Department of Pharmacology, Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, SP, Brazil
| | - C M Ribeiro
- Department of Pharmacology, Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, SP, Brazil
| | - M R Dias-da-Silva
- Department of Medicine, Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, SP, Brazil
| | - E J R Silva
- Department of Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista 'Júlio de Mesquita Filho', Botucatu, SP, Brazil
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40
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New changes in pregnancy and lactation labelling: Review of dermatologic drugs. Int J Womens Dermatol 2019; 5:216-226. [PMID: 31700976 PMCID: PMC6831768 DOI: 10.1016/j.ijwd.2019.05.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 04/15/2019] [Accepted: 05/02/2019] [Indexed: 12/24/2022] Open
Abstract
Background The U.S. Food and Drug Administration has published new pregnancy and lactation labelling rules that set standards on the presentation of information with regard to drug usage during pregnancy and breastfeeding, as well as the effects on fertility. These guidelines became effective June 30, 2015, and classified the risks of using prescription drugs during pregnancy in three detailed subsections: Pregnancy, Lactation, and Females and Males of Reproductive Potential. These sections describe the risks within a real-world context of caring for these patients. Objective In this study, we reclassified and categorized drugs and treatments commonly used in dermatology according to these new guidelines. Methods We performed a search of the medical literature about the use of relevant prescription drugs during pregnancy and breastfeeding and their effect on fertility. The search included prospective and retrospective studies, review articles from PubMed-indexed journals (from inception to November 2018), U.S. Food and Drug Administration records, pregnancy exposure registries, relevant information and studies provided in drug labeling by companies, and updated pharmacologic texts and guidelines up to 2018. Results Topical immunomodulators, systemic immunomodulators (including biologics), systemic antipruritic agents, antimicrobials, as well as acne, hair, and cosmetic agents were included. We have made best attempts to review and consolidate existing and new data and include them in our guide. Conclusion This new narrative format facilitates prescribing by considering a variety of factors. One previously overlooked aspect was the impact on the reproductive potential of both male and female patients. Rather than depending on overly simplistic letter risk categories, dermatologists will now need to make prescribing decisions based on each patient and the information provided, which will allow for better decision making and patient care.
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41
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Grosen A, Bungum M, Christensen LA, Cordelli E, Larsen OH, Leter G, Julsgaard M, Vestergaard T, Villani P, Hvas CL, Kelsen J. Semen Quality and Sperm DNA Integrity in Patients With Severe Active Inflammatory Bowel Disease and Effects of Tumour Necrosis Factor-alpha Inhibitors. J Crohns Colitis 2019; 13:564-571. [PMID: 30500868 DOI: 10.1093/ecco-jcc/jjy198] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS The impact of severe inflammation on semen quality, including sperm DNA integrity, in men with inflammatory bowel disease [IBD] is unknown, as are the potential effects of anti-tumour necrosis factor-alpha [TNF-alpha] therapy. We investigated the influence of severe active IBD and anti-TNF-alpha treatment on semen quality. METHODS We prospectively included 20 patients admitted with severe active IBD. Further, 19 patients who initiated and 17 who stopped anti-TNF-alpha therapy were included. Semen samples were obtained during active disease, and on/off treatment. For paired comparisons, samples were collected not less than 3 months after achieving remission, after treatment initiation, or after treatment cessation. Sperm DNA Fragmentation Index [DFI], concentration, morphology, and motility were evaluated. Sex hormones and seminal plasma anti-TNF-alpha drug levels were measured. RESULTS In patients with severe disease, progressive sperm motility was impaired and increased significantly [from 28.4% to 37.4%, p = 0.045] during remission. There was no difference in DFI [12.5% versus 12.0%, p = 0.55], concentration [55.0 mill/ml versus 70.0 mill/ml, p = 0.39], or normal morphology [4.7% versus 5.1%, p = 0.51] in these patients. During active disease, testosterone was decreased, and normalised after obtaining remission. Patients who started anti-TNF-alpha therapy had a statistically significant, but clinically irrelevant, reduction in DFI after treatment initiation [12.8% versus 10.0%, p = 0.02]. All other semen parameters were unaffected by therapy. Anti-TNF-alpha drugs were excreted in negligible amounts in semen. CONCLUSIONS Severe active IBD reduces progressive sperm motility and testosterone levels, but sperm DNA integrity is unaffected by active disease. Anti-TNF-alpha therapy does not impair sperm quality.
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Affiliation(s)
- Anne Grosen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Mona Bungum
- Reproductive Medicine Centre, Skaane University Hospital, Malmoe, Sweden
| | - Lisbet Ambrosius Christensen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.,Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Eugenia Cordelli
- Laboratory of Biosafety and Risk Assessment, ENEA, Casaccia Research Centre, Rome, Italy
| | - Ole Halfdan Larsen
- Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
| | - Giorgio Leter
- Laboratory of Biosafety and Risk Assessment, ENEA, Casaccia Research Centre, Rome, Italy
| | - Mette Julsgaard
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Thea Vestergaard
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Paola Villani
- Laboratory of Biosafety and Risk Assessment, ENEA, Casaccia Research Centre, Rome, Italy
| | - Christian Lodberg Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Jens Kelsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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Haidl G, Haidl F, Allam JP, Schuppe HC. Therapeutic options in male genital tract inflammation. Andrologia 2018; 51:e13207. [DOI: 10.1111/and.13207] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 09/25/2018] [Accepted: 10/15/2018] [Indexed: 12/21/2022] Open
Affiliation(s)
- Gerhard Haidl
- Andrology Unit, Department of Dermatology and Allergy; University Hospital Bonn; Bonn Germany
| | - Friederike Haidl
- Department of Urology; University Hospital Cologne; Cologne Germany
| | - Jean-Pierre Allam
- Andrology Unit, Department of Dermatology and Allergy; University Hospital Bonn; Bonn Germany
| | - Hans-Christian Schuppe
- Department of Urology, Pediatric Urology and Andrology; Justus Liebig University; Giessen Germany
- Hessian Centre of Reproductive Medicine; Justus Liebig University; Giessen Germany
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43
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Pascarelli NA, Fioravanti A, Moretti E, Guidelli GM, Mazzi L, Collodel G. The effects in vitro of TNF-α and its antagonist 'etanercept' on ejaculated human sperm. Reprod Fertil Dev 2018; 29:1169-1177. [PMID: 27185240 DOI: 10.1071/rd16090] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2015] [Accepted: 03/16/2016] [Indexed: 12/22/2022] Open
Abstract
Tumour necrosis factor (TNF)-α is primarily involved in the regulation of cell proliferation and apoptosis; in addition it possesses pro-inflammatory properties. Anti-TNF-α strategies involve either administration of anti-TNF-α antibody or soluble TNF receptor to mop up circulating TNF-α. Etanercept, a recombinant human TNF-α receptor, was found to be effective in the treatment of rheumatoid arthritis. The impact of TNF-α inhibitors on human fertility is of notable interest. This in vitro study investigated the effect of different concentrations of TNF-α and etanercept used alone or in combination on sperm viability, motility, mitochondrial function, percentage of apoptosis and chromatin integrity in swim-up selected human spermatozoa. A negative effect of TNF-α (300 and 500ng mL-1) and etanercept (from 800µg mL-1 to 2000µg mL-1) individually on sperm viability, motility, mitochondrial function, percentage of apoptotic spermatozoa and sperm DNA integrity was demonstrated. However, at concentrations of 100 and 200µg mL-1, etanercept can block, in a significant way, the toxic effects of TNF-α (500ng mL-1) on studied sperm characteristics. Our results confirm that TNF-α has a detrimental effect on sperm function and suggest, for the first time, that etanercept may counteract the in vitro toxic action of TNF-α. This data appears to be quite promising, although further studies, both in vivo and in vitro, are needed to understand the exact mechanism of action of TNF-α and TNF-α antagonists on sperm function.
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Affiliation(s)
- Nicola A Pascarelli
- Rheumatology Unit, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Viale Bracci, 14, 53100, Siena, Italy
| | - Antonella Fioravanti
- Rheumatology Unit, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Viale Bracci, 14, 53100, Siena, Italy
| | - Elena Moretti
- Department of Molecular and Developmental Medicine, University of Siena, Policlinico Le Scotte, Viale Bracci, 14, 53100, Siena, Italy
| | - Giacomo M Guidelli
- Rheumatology Unit, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Viale Bracci, 14, 53100, Siena, Italy
| | - Lucia Mazzi
- Department of Molecular and Developmental Medicine, University of Siena, Policlinico Le Scotte, Viale Bracci, 14, 53100, Siena, Italy
| | - Giulia Collodel
- Department of Molecular and Developmental Medicine, University of Siena, Policlinico Le Scotte, Viale Bracci, 14, 53100, Siena, Italy
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44
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Ma J, Fan Y, Zhang J, Feng S, Hu Z, Qiu W, Long K, Jin L, Tang Q, Wang X, Zhou Q, Gu Y, Xiao W, Liu L, Li X, Li M. Testosterone-Dependent miR-26a-5p and let-7g-5p Act as Signaling Mediators to Regulate Sperm Apoptosis via Targeting PTEN and PMAIP1. Int J Mol Sci 2018; 19:E1233. [PMID: 29670053 PMCID: PMC5979296 DOI: 10.3390/ijms19041233] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Revised: 04/12/2018] [Accepted: 04/13/2018] [Indexed: 02/07/2023] Open
Abstract
Recent evidence suggests that testosterone deficiency can dramatically decrease the quality of sperm. MicroRNAs (miRNAs) are conserved mediators of post-transcriptional gene regulation in eukaryotes. However, the systemic regulation and function of miRNAs in sperm quality decline induced by testosterone deficiency has not been investigated. Here, we found that the sperm apoptosis was significantly enhanced and the sperm motility was dramatically decreased in hemicastrated pigs. We then used small RNA sequencing to detect miRNA profiles of sperm from pigs with prepubertal hemicastration (HC) and compared them with control libraries. We identified 16 differentially expressed (DE) miRNAs between the sperm of prepubertal HC and control (CT) pigs. Functional enrichment analysis indicated that the target genes of these DE miRNAs were mainly enriched in apoptosis-related pathways including the p53, mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) pathways. Furthermore, gain- and loss-of-function analyses demonstrated potential anti-apoptotic effects of the DE miRNAs miR-26a-5p and let-7g-5p on sperm cells. The luciferase reporter assay confirmed that PTEN and PMAIP1 are targets of miR-26a-5p and let-7g-5p, respectively. Spearman’s correlation analysis revealed significantly positive correlations between the sperm and its corresponding seminal plasma exosomes regarding the miRNA expression levels. In conclusion, testosterone deficiency-induced changes in the miRNA components of seminal plasma exosomes secreted by the genital tract may partially elucidate sperm miRNAome alterations, which are further responsible for the decline of sperm motility.
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Affiliation(s)
- Jideng Ma
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
| | - Yu Fan
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
| | - Jinwei Zhang
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
| | - Siyuan Feng
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
| | - Zihui Hu
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
| | - Wanling Qiu
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
| | - Keren Long
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
| | - Long Jin
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
| | - Qianzi Tang
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
| | - Xun Wang
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
| | - Qi Zhou
- Chengdu Polytechnic, Chengdu 610041, China.
| | - Yiren Gu
- Animal Breeding and Genetics Key Laboratory of Sichuan Province, Pig Science Institute, Sichuan Animal Science Academy, Chengdu 610066, China.
| | - Weihang Xiao
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
| | - Lingyan Liu
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
| | - Xuewei Li
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
| | - Mingzhou Li
- Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
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Elweza AE, Ezz MA, Acosta TJ, Talukder AK, Shimizu T, Hayakawa H, Shimada M, Imakawa K, Zaghloul AH, Miyamoto A. A proinflammatory response of bovine endometrial epithelial cells to active sperm in vitro. Mol Reprod Dev 2018; 85:215-226. [DOI: 10.1002/mrd.22955] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 12/15/2017] [Accepted: 01/03/2018] [Indexed: 02/03/2023]
Affiliation(s)
- Ahmed E. Elweza
- Graduate School of Animal and Food Hygiene; Obihiro University of Agriculture and Veterinary Medicine; Obihiro Japan
- Faculty of Veterinary Medicine; Department of Theriogenology; University of Sadat City; Sadat City Egypt
| | - Mohamed A. Ezz
- Graduate School of Animal and Food Hygiene; Obihiro University of Agriculture and Veterinary Medicine; Obihiro Japan
- Faculty of Veterinary Medicine; Department of Theriogenology; Mansoura University; Mansoura Egypt
| | - Tomas J. Acosta
- Field Center of Animal Science and Agriculture; Obihiro University of Agriculture and Veterinary Medicine; Obihiro Japan
| | - Anup K. Talukder
- Graduate School of Animal and Food Hygiene; Obihiro University of Agriculture and Veterinary Medicine; Obihiro Japan
- Department of Gynecology; Obstetrics and Reproductive Health; Bangabandhu Sheikh Mujibur Rahman Agricultural University; Gaipur Bangladesh
| | - Takashi Shimizu
- Graduate School of Animal and Food Hygiene; Obihiro University of Agriculture and Veterinary Medicine; Obihiro Japan
| | | | - Masayuki Shimada
- Graduate School of Biosphere Science; Hiroshima University; Higashi-Hiroshima Japan
| | - Kazuhiko Imakawa
- Animal Resource Science Center; Graduate School of Agricultural and Life Sciences; The University of Tokyo; Ibaraki Japan
| | - Ahmed H. Zaghloul
- Faculty of Veterinary Medicine; Department of Theriogenology; University of Sadat City; Sadat City Egypt
| | - Akio Miyamoto
- Graduate School of Animal and Food Hygiene; Obihiro University of Agriculture and Veterinary Medicine; Obihiro Japan
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Silva EJR, Ribeiro CM, Mirim AFM, Silva AAS, Romano RM, Hallak J, Avellar MCW. Lipopolysaccharide and lipotheicoic acid differentially modulate epididymal cytokine and chemokine profiles and sperm parameters in experimental acute epididymitis. Sci Rep 2018; 8:103. [PMID: 29311626 PMCID: PMC5758752 DOI: 10.1038/s41598-017-17944-4] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Accepted: 11/28/2017] [Indexed: 11/09/2022] Open
Abstract
Bacterial infections are the most prevalent etiological factors of epididymitis, a commonly diagnosed inflammatory disease in the investigation of male infertility factors. The influence of early pathogenic mechanisms at play during bacterial epididymitis on reproductive outcomes is little understood. We report here that experimental epididymitis induced in rats by Gram-negative (LPS) and Gram-positive (LTA) bacterial products resulted in differential patterns of acute inflammation in the cauda epididymis. LPS elicited a strong inflammatory reaction, as reflected by upregulation of levels of mRNA for seven inflammatory mediators (Il1b, Tnf, Il6, Ifng, Il10, Nos2 and Nfkbia), and tissue concentration of six cytokines/chemokines (IL1A, IL1B, IL6, IL10, CXCL2 and CCL2) within the first 24 h post-treatment. Conversely, LTA induced downregulation of one (Nfkbia) and upregulation of six (Il1b, Il6, Nos2, Il4 Il10 and Ptgs1) inflammatory gene transcripts, whereas increased the tissue concentration of three cytokines/chemokines (IL10, CXCL2 and CCL2). The stronger acute inflammatory response induced by LPS correlated with a reduction of epididymal sperm count and transit time that occurred at 1, 7, and 15 days post-treatment. Our study provides evidence that early epididymal inflammatory signaling events to bacterial activators of innate immunity may contribute to the detrimental effects of epididymitis upon male fertility.
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Affiliation(s)
- Erick J R Silva
- Section of Experimental Endocrinology, Department of Pharmacology, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, SP, 04044-020, Brazil.
- Department of Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista "Júlio de Mesquita Filho", Botucatu, SP, 18618-869, Brazil.
| | - Camilla M Ribeiro
- Section of Experimental Endocrinology, Department of Pharmacology, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, SP, 04044-020, Brazil
| | - André F M Mirim
- Section of Experimental Endocrinology, Department of Pharmacology, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, SP, 04044-020, Brazil
| | - Alan A S Silva
- Department of Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista "Júlio de Mesquita Filho", Botucatu, SP, 18618-869, Brazil
| | - Renata M Romano
- Section of Experimental Endocrinology, Department of Pharmacology, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, SP, 04044-020, Brazil
- Department of Pharmacy, State University of Centro-Oeste, Guarapuava, PR, 85040-080, Brazil
| | - Jorge Hallak
- Androscience, Science and Innovation Center in Andrology, São Paulo, SP, 03178-200, Brazil
- Reproductive Toxicology Unity, Department of Pathology and Division of Urology, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, SP, 01246-903, Brazil
| | - Maria Christina W Avellar
- Section of Experimental Endocrinology, Department of Pharmacology, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, SP, 04044-020, Brazil.
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47
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Fan W, Xu Y, Liu Y, Zhang Z, Lu L, Ding Z. Obesity or Overweight, a Chronic Inflammatory Status in Male Reproductive System, Leads to Mice and Human Subfertility. Front Physiol 2018; 8:1117. [PMID: 29354072 PMCID: PMC5758580 DOI: 10.3389/fphys.2017.01117] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Accepted: 12/18/2017] [Indexed: 12/18/2022] Open
Abstract
Obesity is frequently accompanied with chronic inflammation over the whole body and is always associated with symptoms that include those arising from metabolic and vascular alterations. On the other hand, the chronic inflammatory status in the male genital tract may directly impair spermatogenesis and is even associated with male subfertility. However, it is still unclear if the chronic inflammation induced by obesity damages spermatogenesis in the male genital tract. To address this question, we used a high fat diet (HFD) induced obese mouse model and recruited obese patients from the clinic. We detected increased levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and NOD-like receptor family pyrin domain containing-3 (NLRP3) in genital tract tissues including testis, epididymis, seminal vesicle, prostate, and serum from obese mice. Meanwhile, the levels of immunoglobulin G (IgG) and corticosterone were significantly higher than those in the control group in serum. Moreover, signal factors regulated by TNF-α, i.e., p38, nuclear factor-κB (NF-κB), Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and their phosphorylated status, and inflammasome protein NLRP3 were expressed at higher levels in the testis. For overweight and obese male patients, the increased levels of TNF-α and IL-6 were also observed in their seminal plasma. Furthermore, there was a positive correlation between the TNF-α and IL-6 levels and BMI whereas they were inversely correlated with the sperm concentration and motility. In conclusion, impairment of male fertility may stem from a chronic inflammatory status in the male genital tract of obese individuals.
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Affiliation(s)
- Weimin Fan
- Shanghai Key Laboratory for Reproductive Medicine, Department of Histology Embryology, Genetics and Developmental Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Reproductive Medicine Center, Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yali Xu
- Shanghai Key Laboratory for Reproductive Medicine, Department of Histology Embryology, Genetics and Developmental Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yue Liu
- Shanghai Key Laboratory for Reproductive Medicine, Department of Histology Embryology, Genetics and Developmental Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhengqing Zhang
- The Laboratory of Clinical Medicine, Shanghai No.9 People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Liming Lu
- Laboratory of Immune Regulation, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhide Ding
- Shanghai Key Laboratory for Reproductive Medicine, Department of Histology Embryology, Genetics and Developmental Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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48
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van Son M, Tremoen NH, Gaustad AH, Myromslien FD, Våge DI, Stenseth EB, Zeremichael TT, Grindflek E. RNA sequencing reveals candidate genes and polymorphisms related to sperm DNA integrity in testis tissue from boars. BMC Vet Res 2017; 13:362. [PMID: 29183316 PMCID: PMC5706377 DOI: 10.1186/s12917-017-1279-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 11/16/2017] [Indexed: 11/17/2022] Open
Abstract
Background Sperm DNA is protected against fragmentation by a high degree of chromatin packaging. It has been demonstrated that proper chromatin packaging is important for boar fertility outcome. However, little is known about the molecular mechanisms underlying differences in sperm DNA fragmentation. Knowledge of sequence variation influencing this sperm parameter could be beneficial in selecting the best artificial insemination (AI) boars for commercial production. The aim of this study was to identify genes differentially expressed in testis tissue of Norwegian Landrace and Duroc boars, with high and low sperm DNA fragmentation index (DFI), using transcriptome sequencing. Results Altogether, 308 and 374 genes were found to display significant differences in expression level between high and low DFI in Landrace and Duroc boars, respectively. Of these genes, 71 were differentially expressed in both breeds. Gene ontology analysis revealed that significant terms in common for the two breeds included extracellular matrix, extracellular region and calcium ion binding. Moreover, different metabolic processes were enriched in Landrace and Duroc, whereas immune response terms were common in Landrace only. Variant detection identified putative polymorphisms in some of the differentially expressed genes. Validation showed that predicted high impact variants in RAMP2, GIMAP6 and three uncharacterized genes are particularly interesting for sperm DNA fragmentation in boars. Conclusions We identified differentially expressed genes between groups of boars with high and low sperm DFI, and functional annotation of these genes point towards important biochemical pathways. Moreover, variant detection identified putative polymorphisms in the differentially expressed genes. Our results provide valuable insights into the molecular network underlying DFI in pigs. Electronic supplementary material The online version of this article (10.1186/s12917-017-1279-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
| | - Nina Hårdnes Tremoen
- Department of Natural Sciences and Technology, Inland Norway University of Applied Sciences, 2318, Hamar, Norway.,Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Faculty of Biosciences, Norwegian University of Life Sciences, 1432, Ås, Norway
| | - Ann Helen Gaustad
- Topigs Norsvin, 2317, Hamar, Norway.,Department of Natural Sciences and Technology, Inland Norway University of Applied Sciences, 2318, Hamar, Norway
| | - Frøydis Deinboll Myromslien
- Department of Natural Sciences and Technology, Inland Norway University of Applied Sciences, 2318, Hamar, Norway
| | - Dag Inge Våge
- Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Faculty of Biosciences, Norwegian University of Life Sciences, 1432, Ås, Norway
| | - Else-Berit Stenseth
- Department of Natural Sciences and Technology, Inland Norway University of Applied Sciences, 2318, Hamar, Norway
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49
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Wu H, Wang D, Meng Y, Ning H, Liu X, Xie Y, Cui L, Wang S, Xu X, Peng R. Activation of TLR signalling regulates microwave radiation-mediated impairment of spermatogenesis in rat testis. Andrologia 2017; 50. [PMID: 28782295 DOI: 10.1111/and.12828] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/09/2017] [Indexed: 02/06/2023] Open
Affiliation(s)
- H. Wu
- Department of Pathology; Navy General Hospital; Beijing China
| | - D. Wang
- Beijing Institute of Radiation Medicine; Beijing China
| | - Y. Meng
- Department of Pathology; Navy General Hospital; Beijing China
| | - H. Ning
- Department of Pathology; Navy General Hospital; Beijing China
| | - X. Liu
- Department of Pathology; Navy General Hospital; Beijing China
| | - Y. Xie
- Beijing Institute of Radiation Medicine; Beijing China
| | - L. Cui
- Beijing Institute of Radiation Medicine; Beijing China
| | - S. Wang
- Beijing Institute of Radiation Medicine; Beijing China
| | - X. Xu
- Beijing Institute of Radiation Medicine; Beijing China
| | - R. Peng
- Beijing Institute of Radiation Medicine; Beijing China
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50
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Heppt F, Colsman A, Maronna A, Uslu U, Heppt MV, Kiesewetter F, Sticherling M. Influence of TNF-alpha inhibitors and fumaric acid esters on male fertility in psoriasis patients. J Eur Acad Dermatol Venereol 2017; 31:1860-1866. [PMID: 28557008 DOI: 10.1111/jdv.14364] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Accepted: 04/19/2017] [Indexed: 12/29/2022]
Abstract
OBJECTIVE Is there any influence of a therapy with TNF-alpha inhibitors or fumaric acid esters and of disease activity status on male fertility and sperm quality in patients with psoriasis? METHODS In this monocentric, open-label, prospective study, semen samples were collected from patients receiving either TNF-alpha inhibitors or fumaric acid esters for moderate-to-severe plaque psoriasis. Semen was analysed at baseline before onset of the systemic therapy and monitored every 3 months under therapy. Sperm parameters were assessed according to the current WHO definitions. RESULTS In total, 101 semen specimens from 27 patients were obtained. Mean Psoriasis Area and Severity Index (PASI) score at baseline was 11.05. Only 14.8% of patients showed a normozoospermia without any other abnormal seminal values. 85.2% of patients had at least one sperm/seminal abnormality, including two patients showing an azoospermia. Interestingly, 48.1% showed sperm parameters indicative of genital tract inflammation. Therapy with TNF-alpha inhibitors or fumaric acid esters did not have any negative effects on relevant sperm parameters such as mean total sperm number, sperm concentration, total and progressive motility. No major gonadal dysfunction was observed in any patient. CONCLUSION At baseline, many patients with psoriasis showed abnormal semen/sperm parameters and remarkably elevated leukocytes and values of seminal polymorphonuclear elastase, indicating a genital tract inflammation. Thus, genital tract inflammation may represent an important comorbidity of psoriasis, little attention paid to so far. Regarding treatment with TNF-alpha inhibitors or fumaric acid esters, no major negative (side-) effects on sperm quality were observed.
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Affiliation(s)
- F Heppt
- Department of Dermatology, University Hospital of Erlangen, Erlangen, Germany
| | - A Colsman
- Department of Dermatology, University Hospital of Erlangen, Erlangen, Germany
| | - A Maronna
- Department of Dermatology, University Hospital of Erlangen, Erlangen, Germany
| | - U Uslu
- Department of Dermatology, University Hospital of Erlangen, Erlangen, Germany
| | - M V Heppt
- Department of Dermatology and Allergy, Munich University Hospital (LMU), Munich, Germany
| | - F Kiesewetter
- Department of Dermatology, University Hospital of Erlangen, Erlangen, Germany
| | - M Sticherling
- Department of Dermatology, University Hospital of Erlangen, Erlangen, Germany
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