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Babolhekami H, Ebrahimzadeh-Bideskan A, Eshtad E, Karimi S. The Effect of Scrotal PRP Injection on Testes Function and Spermatogenesis Resumed in Azoospermia Mice Model Caused by Chronic Hyperthermia. Reprod Sci 2025:10.1007/s43032-025-01824-8. [PMID: 40032806 DOI: 10.1007/s43032-025-01824-8] [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: 10/19/2024] [Accepted: 02/13/2025] [Indexed: 03/05/2025]
Abstract
Infertility is an important health concern that affects around 15% of couples, 40-50% of infertile cases are because of malefactors. Azoospermia is known as one of the important causes of male infertility. PRP is an autologous source of growth factors used in various therapeutic strategies. In the present study, PRP was injected into mice scrotum, after induced azoospermia caused by scrotal hyperthermia, and then therapeutic effects were evaluated. 24 adult male mice were divided into 4 groups: Control, Azoospermia (model induced by scrotal hyperthermia every other day after anesthesia for 35 days), and ketamine/xylazine (Ket/Xi) (to assess the probable effect of anesthesia), PRP (injected 10ul of PRP in the scrotum of azoospermia mice) after 16 days animals were anesthetized and sacrificed. Plasma testosterone, seminiferous diameter, oxidative stress, and sperm parameters were evaluated. Plasma testosterone level in the Azoospermia group significantly decreased and PRP treatment improved it. Also, the testicular tissue showed impairment, and oxidative stress levels increased in the testes in the Azoospermia group and PRP treatment ameliorated them. Spermatogenesis completely arrested after scrotal hyperthermia that after treatment with PRP, resumed. PRP injection in the scrotum resumed spermatogenesis and increased the production of testosterone, reduced the oxidative stress level in the testicular tissue, and resumed sperm production. PRP shows promise in promoting testicular recovery following hyperthermia-induced damage.
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Affiliation(s)
- Hanieh Babolhekami
- Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Azadi Sq, Vakilabad Blvd, Mashhad, Iran
- Sterility and Reproductive Biology Research Center, Emam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Alireza Ebrahimzadeh-Bideskan
- Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Azadi Sq, Vakilabad Blvd, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Sterility and Reproductive Biology Research Center, Emam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elahe Eshtad
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Sterility and Reproductive Biology Research Center, Emam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sareh Karimi
- Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Azadi Sq, Vakilabad Blvd, Mashhad, Iran.
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
- Sterility and Reproductive Biology Research Center, Emam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
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Al Turki HA, Al-Suhaibani SS, AlShamlan DY, Ahmed A, Alhawaj HA. Autologous Bone Marrow-Derived Mesenchymal Stem Cells in the Reversal of Unobstructed Azoospermia in Rats. Stem Cells Cloning 2024; 17:33-39. [PMID: 39464173 PMCID: PMC11512562 DOI: 10.2147/sccaa.s481267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 10/08/2024] [Indexed: 10/29/2024] Open
Abstract
Background and Objective Non-obstructive azoospermia (NOA) is an important cause of male infertility. This study is being proposed to assess the efficacy of autologous bone marrow-derived mesenchymal stem cells (MSCs) in the reversal of busulfan-induced NOA in rats. Methods Twenty adult 3-month-old male rats were divided into two groups: a control group and a study group. In the study group, bone marrow was aspirated to culture MSCs. NOA was created by stopping endogenous spermatogenesis in all the animals by injecting two doses of busulfan 10 mg/kg body weight with a 3 week interval. Four weeks after the last dose of busulfan, two animals were euthanized and the testes were studied histologically to confirm complete azoospermia. In the study group, five million MSCs in 1 mL normal saline were injected into seminiferous tubules; and in the control group, 1 mL of normal saline was injected. After 4 weeks of MSC injection, all the rats were euthanized and epididymis tails and testes were harvested and sent for measurement of serological indices, including luminal, cellular, and total diameters, luminal, cellular, and cross-sectional areas, number of tubules per unit area of testis, numerical density of the tubules, and spermatogenesis index, pre- and post-MSC transplantation. Results The effect of busulfan on the testicular tissue was universally devastating. In the control group, there was variable length and width of markedly necrotic seminiferous tubules, whereas in the group treated with autologous bone marrow-derived MSCs there was variable height of germinal epithelium in seminiferous tubules, with active spermatogenesis, showing spermatogonia, spermatocytes, and sperm. Conclusion MSC injection in the testis has the potential to reverse the testicular function of spermatogenesis after cytotoxic therapy. Human trials should be undertaken to confirm our findings and bring the results into clinical practice.
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Affiliation(s)
- Haifa A Al Turki
- Department of Obstetrics and Gynecology, Imam AbdulRahman Bin Faisal University, Dammam and King Fahd Hospital of the University, AlKhobar, Saudi Arabia
| | - Shaheed S Al-Suhaibani
- Department of Urology, Imam AbdulRahman Bin Faisal University, Dammam and King Fahd Hospital of the University, AlKhobar, Saudi Arabia
| | - Danah Y AlShamlan
- Department of Obstetrics and Gynecology, Imam AbdulRahman Bin Faisal University, Dammam and King Fahd Hospital of the University, AlKhobar, Saudi Arabia
| | - Ayesha Ahmed
- Department of Pathology, Imam AbdulRahman Bin Faisal University, Dammam and King Fahd Hospital of the University, AlKhobar, Saudi Arabia
| | - Hussain A Alhawaj
- Department of Animal House, Imam AbdulRahman Bin Faisal University, Dammam and King Fahd Hospital of the University, AlKhobar, Saudi Arabia
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Gao S, Yang J, Chen D, Min X, Fan C, Zhang P, Wang Q, Li Z, Cai W. Noninvasive Prediction of Sperm Retrieval Using Diffusion Tensor Imaging in Patients with Nonobstructive Azoospermia. J Imaging 2023; 9:182. [PMID: 37754946 PMCID: PMC10532242 DOI: 10.3390/jimaging9090182] [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: 07/07/2023] [Revised: 09/04/2023] [Accepted: 09/06/2023] [Indexed: 09/28/2023] Open
Abstract
Microdissection testicular sperm extraction (mTESE) is the first-line treatment plan for nonobstructive azoospermia (NOA). However, studies reported that the overall sperm retrieval rate (SRR) was 43% to 63% among men with NOA, implying that nearly half of the patients fail sperm retrieval. This study aimed to evaluate the diagnostic performance of parameters derived from diffusion tensor imaging (DTI) in predicting SRR in patients with NOA. Seventy patients diagnosed with NOA were enrolled and classified into two groups based on the outcome of sperm retrieval during mTESE: success (29 patients) and failure (41 patients). Scrotal magnetic resonance imaging was performed, and the DTI parameters, including mean diffusivity and fractional anisotropy, were analyzed between groups. The results showed that there was a significant difference in mean diffusivity values between the two groups, and the area under the curve for mean diffusivity was calculated as 0.865, with a sensitivity of 72.2% and a specificity of 97.5%. No statistically significant difference was observed in fractional anisotropy values and sex hormone levels between the two groups. This study demonstrated that the mean diffusivity value might serve as a useful noninvasive imaging marker for predicting the SRR of NOA patients undergoing mTESE.
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Affiliation(s)
- Sikang Gao
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (S.G.); (X.M.); (C.F.); (P.Z.); (Q.W.); (Z.L.)
| | - Jun Yang
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China;
| | - Dong Chen
- Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China;
| | - Xiangde Min
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (S.G.); (X.M.); (C.F.); (P.Z.); (Q.W.); (Z.L.)
| | - Chanyuan Fan
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (S.G.); (X.M.); (C.F.); (P.Z.); (Q.W.); (Z.L.)
| | - Peipei Zhang
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (S.G.); (X.M.); (C.F.); (P.Z.); (Q.W.); (Z.L.)
| | - Qiuxia Wang
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (S.G.); (X.M.); (C.F.); (P.Z.); (Q.W.); (Z.L.)
| | - Zhen Li
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (S.G.); (X.M.); (C.F.); (P.Z.); (Q.W.); (Z.L.)
| | - Wei Cai
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (S.G.); (X.M.); (C.F.); (P.Z.); (Q.W.); (Z.L.)
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Rusevski A, Plaseska-Karanfilska D, Davalieva K. Proteomics of azoospermia: Towards the discovery of reliable markers for non-invasive diagnosis. Proteomics Clin Appl 2023; 17:e2200060. [PMID: 36177695 DOI: 10.1002/prca.202200060] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/12/2022] [Accepted: 09/21/2022] [Indexed: 01/28/2023]
Abstract
PURPOSE Azoospermia, as the most severe form of male infertility, no longer indicates sterility due to modern medical advancements. The current diagnostic procedure based on testicular biopsy has several drawbacks which urges the development of novel, non-invasive diagnostic procedures based on biomarkers. In the last two decades, there have been many proteomics studies investigating potential azoospermia biomarkers. In this review, we aimed to provide a critical evaluation of these studies. EXPERIMENTAL DESIGN Published articles were gathered by systematic literature search using Pubmed, Science Direct, and Google Scholar databases until March 2022 and were further preselected to include only studies on human samples. RESULTS A detailed review of these studies encompassed the proteomics platforms, sources of material, proposed candidate biomarkers, and their potential diagnostic specificity and sensitivity. In addition, emphasis was put on the top, most identified and validated biomarker candidates and their potential for discriminating azoospermia types and subtypes as well as predicting sperm retrieval success rate. CONCLUSIONS Proteomics research of azoospermia has laid the groundwork for the development of a more streamlined biomarker testing. The future research should be focused on well-designed studies including samples from all types/subtypes as well as further testing of the most promising biomarkers identified so far.
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Affiliation(s)
- Aleksandar Rusevski
- Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, North Macedonia
| | - Dijana Plaseska-Karanfilska
- Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, North Macedonia
| | - Katarina Davalieva
- Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, North Macedonia
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Li JP, Du CQ, Liu ZB, Zhang FB, Li LJ, Wu JG, Tian YH, Liang ZY, Chen C, Jin F. Development and validation predictive models of sperm retrieval for azoospermic men undergoing testicular sperm aspiration: a multicentre, retrospective, cohort study. J Assist Reprod Genet 2022; 39:1779-1787. [PMID: 35870097 PMCID: PMC9428087 DOI: 10.1007/s10815-022-02531-y] [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: 02/21/2022] [Accepted: 05/26/2022] [Indexed: 01/19/2023] Open
Abstract
PURPOSE Testicular sperm aspiration (TESA) is widely used to retrieve sperm from testis. Diagnostic testicular biopsy should not be routinely performed for azoospermia. Therefore, a good predictive model is needed before TESA. METHODS A total of 1972 azoospermia patients constituted the modelling set, and 260 azoospermia patients from two other centres constituted the validation set. An integrated predictive model was built using logistic regression. Receiver operating characteristic (ROC), calibration and decision curve analyses were performed to evaluate the performance of follicle-stimulating hormone (FSH), semen volume, testicular volume and the integrated model. RESULTS The FSH level was the best univariate predictor for successful sperm retrieval (SSR) and was better than semen volume and testicular volume alone (p<0.001, threshold 6.17 IU/L, modelling set area under receiver operating characteristic curve (AUC) 0.80, accuracy 0.79; validation set AUC 0.87, accuracy 0.78). The integrated predictive model had excellent accuracy for predicting SSR (modelling set: AUC 0.93, accuracy 0.89; validation set: AUC 0.96, accuracy: 0.89). Calibration curve analysis indicated that the integrated model calibration was good and better than that of FSH, semen volume and testicular volume alone. Decision curve analysis indicated with a threshold probability between 0.05 and 0.98, the integrated model added more benefit than treating either all or no patients. CONCLUSIONS The integrated model has excellent discrimination and good calibration. It can help azoospermic men make better decisions before TESA. It should be noted that TESA is not the first-line treatment for non-obstructive azoospermia because of a low sperm retrieval rate.
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Affiliation(s)
- Jing-Ping Li
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China, 310006
| | - Cong-Qi Du
- Reproductive Medicine Centre, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China
| | - Zu-Bo Liu
- Reproductive Medicine Centre, Jinhua People's Hospital, Jinhua, People's Republic of China
| | - Feng-Bin Zhang
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China, 310006
| | - Le-Jun Li
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China, 310006
| | - Jing-Gen Wu
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China, 310006
| | - Yong-Hong Tian
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China, 310006
| | - Zhong-Yan Liang
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China, 310006
| | - Chong Chen
- Department of Ultrasound, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China
| | - Fan Jin
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China, 310006.
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Çitli Ş, Ceylan AC, Erdemir F. Investigation of sub-chromosomal changes in males with idiopathic azoospermia by chromosomal microarray analysis. Andrologia 2022; 54:e14489. [PMID: 35672008 DOI: 10.1111/and.14489] [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: 04/07/2022] [Revised: 05/21/2022] [Accepted: 05/26/2022] [Indexed: 11/26/2022] Open
Abstract
Azoospermia consists of a significant proportion of infertility aetiology in males. Although known genetic abnormalities may explain roughly the third of infertility cases, the exact aetiology is still unclear. Chromosomal microarrays are widely used to detect sub chromosomal abnormalities (e.g., microdeletions and microduplications). This study aimed to investigate aetiology in patients with idiopathic azoospermia by using the chromosomal microarray method to detect possible sub chromosomal changes. Twenty-eight patients (with a mean age of 30.4 ± 9 years) that had been diagnosed with idiopathic azoospermia between January 2019 and December 2020 were included in the study. Genomic DNA isolated from the blood of patients were amplified using polymerase chain reaction and was subjected to chromosomal microarray analysis. A total of six microdeletions were identified as clinically significant: one pathogenic copy number variation (CNV), four likely pathogenic CNVs, and one CNV of unknown clinical significance. However, clinical findings indicated that these microdeletions, with variable expression levels, may affect the spermatogenesis process and induce azoospermia. Future investigations regarding the functional effect of these deletions may contribute to our understanding of azoospermia aetiology.
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Affiliation(s)
- Şenol Çitli
- Department of Medical Genetics, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
| | - Ahmet Cevdet Ceylan
- Department of Medical Genetics, Ankara Yıldırım Beyazıt University, Ankara, Turkey
| | - Fikret Erdemir
- Department of Urology, Faculty of Medicine, Tokat Gaziosmanpasa University, Tokat, Turkey
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Adamczewska D, Słowikowska-Hilczer J, Walczak-Jędrzejowska R. The Fate of Leydig Cells in Men with Spermatogenic Failure. Life (Basel) 2022; 12:570. [PMID: 35455061 PMCID: PMC9028943 DOI: 10.3390/life12040570] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 03/25/2022] [Accepted: 04/08/2022] [Indexed: 11/18/2022] Open
Abstract
The steroidogenic cells in the testicle, Leydig cells, located in the interstitial compartment, play a vital role in male reproductive tract development, maintenance of proper spermatogenesis, and overall male reproductive function. Therefore, their dysfunction can lead to all sorts of testicular pathologies. Spermatogenesis failure, manifested as azoospermia, is often associated with defective Leydig cell activity. Spermatogenic failure is the most severe form of male infertility, caused by disorders of the testicular parenchyma or testicular hormone imbalance. This review covers current progress in knowledge on Leydig cells origin, structure, and function, and focuses on recent advances in understanding how Leydig cells contribute to the impairment of spermatogenesis.
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Affiliation(s)
| | | | - Renata Walczak-Jędrzejowska
- Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, 92-213 Lodz, Poland; (D.A.); (J.S.-H.)
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8
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Testicular sperm characteristics in men with nonobstructive azoospermia and their impact on intracytoplasmic sperm injection outcome. Fertil Steril 2021; 117:522-527. [PMID: 34674828 DOI: 10.1016/j.fertnstert.2021.09.024] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 09/13/2021] [Accepted: 09/16/2021] [Indexed: 01/23/2023]
Abstract
OBJECTIVE To report fertilization and clinical pregnancy rates based on sperm characteristics at the time of intracytoplasmic sperm injection (ICSI) in men with nonobstructive azoospermia (NOA) following microdissection testicular sperm extraction (mTESE). DESIGN Retrospective cohort. SETTING Tertiary hospital. PATIENT(S) Men with NOA undergoing mTESE between 2013 and 2016 who had successful sperm retrieval and subsequent spermatozoa available for ICSI. INTERVENTION(S) Sperm characteristic assessment. MAIN OUTCOME MEASURE(S) Fertilization and clinical pregnancy rates. RESULT(S) One hundred ninety-eight men with NOA and successful mTESE were included. The mean ages of the patients and their partners were 35 ± 8 and 31 ± 5 years, respectively. The overall fertilization rate was 44%, and the clinical pregnancy rate was 38%. The absence of twitching sperm motility and the presence of an acrosome defect were associated with decreased fertilization and clinical pregnancy rates on univariable analysis. On multivariable analysis, the presence of motility was associated with higher fertilization rates and greater odds of clinical pregnancy (odds ratio, 4.37; 95% confidence interval, 1.61-11.85). An abnormal acrosome was associated with reduced odds of pregnancy (odds ratio, 0.40; 95% confidence interval, 0.18-0.85). No specific anomaly or combination of sperm abnormalities precluded fertilization or clinical pregnancy with ICSI. CONCLUSION(S) To our knowledge, this is the first comprehensive study evaluating the importance of sperm characteristics and their impact on ICSI outcomes in men with NOA. The results suggest that no specific defect, including the use of nonmotile testicular spermatozoa, precluded a chance of clinical pregnancy. The study evaluated sperm characteristics at the time of ICSI injection; initial evaluation at the time of retrieval may differ significantly from that of spermatozoa selected for ICSI.
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9
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Achermann APP, Esteves SC. Diagnosis and management of infertility due to ejaculatory duct obstruction: summary evidence. Int Braz J Urol 2021; 47:868-881. [PMID: 33566474 PMCID: PMC8321472 DOI: 10.1590/s1677-5538.ibju.2020.0536] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 07/15/2020] [Indexed: 12/20/2022] Open
Affiliation(s)
- Arnold Peter Paul Achermann
- Departmento de Cirurgia (Disciplina de Urologia), Universidade Estadual de Campinas - UNICAMP, Campinas, SP, Brasil.,ANDROFERT, Clínica de Andrologia e Reprodução Humana, Centro de Referência para Reprodução Masculina, Campinas, SP, Brasil.,Urocore - Centro de Urologia e Fisioterapia Pélvica, Londrina, PR, Brasil
| | - Sandro C Esteves
- Departmento de Cirurgia (Disciplina de Urologia), Universidade Estadual de Campinas - UNICAMP, Campinas, SP, Brasil.,ANDROFERT, Clínica de Andrologia e Reprodução Humana, Centro de Referência para Reprodução Masculina, Campinas, SP, Brasil
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10
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Sabetian S, Zarei M, Jahromi BN, Morowvat MH, Tabei SMB, Cava C. Exploring the dysregulated mRNAs-miRNAs-lncRNAs interactions associated to idiopathic non-obstructive azoospermia. J Biomol Struct Dyn 2021; 40:5956-5964. [PMID: 33499760 DOI: 10.1080/07391102.2021.1875879] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Non-obstructive azoospermia (NOA) is the most clinical problem in case of infertility. About 70% of NOA patients are idiopathic with uncharacterized molecular mechanisms. This study aimed to analyze the possible pathogenic miRNA-target gene interaction and lncRNA-miRNA association involved in NOA. In the current study, differentially expressed (DE) nRNAs, miRNAs and lncRNAs were determined using the microarray dataset and statistical software R. miRNAs-mRNA and miRNA-lncRNA interactions were identified and the base-pair binding between the seed region of miRNAs and complementary nucleotides in 3' UTR of mRNAs were analyzed. The influence of the validated single nucleotide polymorphisms (SNPs) was described by calculating the minimum free energy (MFE) of the interaction. A total of 74 mRNAs, 14 miRNAs, and 10 lncRNAs were identified to have significant differential expression in testicular tissue between patients and the fertile group. Four of the DE-mRNAs and all of the reported DE-miRNAs were upregulated. In addition, all of the represented DE-lncRNAs were showed to be downregulated. miR-509-5p and miR-27b-3p were found to interact with target gene polo-like kinase 1 (PLK1) and Cysteine-rich secretory protein2 (CRISP2), respectively. Rs550967205 (A > G) positioned at 3' UTR CRISP2 and rs544604911 (T > C) located at 3' UTR PLK1, with lowest MFE in miRNA-mRNA interaction, were assumed to have possible pathogenic roles linked to spermatogenesis arrest. The results of the study provide new clues to understand the regulatory roles of miRNAs and lncRNAs in the pathogenesis and diagnosis of idiopathic azoospermia. Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Soudabeh Sabetian
- Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahboubeh Zarei
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Bahia Namavar Jahromi
- Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Obstetrics and Gynecology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | | | - Claudia Cava
- Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), Milan, Italy
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11
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Gunes S, Esteves SC. Role of genetics and epigenetics in male infertility. Andrologia 2020; 53:e13586. [PMID: 32314821 DOI: 10.1111/and.13586] [Citation(s) in RCA: 71] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 03/12/2020] [Indexed: 12/23/2022] Open
Abstract
Male infertility is a complex condition with a strong genetic and epigenetic background. This review discusses the importance of genetic and epigenetic factors in the pathophysiology of male infertility. The interplay between thousands of genes, the epigenetic control of gene expression, and environmental and lifestyle factors, which influence genetic and epigenetic variants, determines the resulting male infertility phenotype. Currently, karyotyping, Y-chromosome microdeletion screening and CFTR gene mutation tests are routinely performed to investigate a possible genetic aetiology in patients with azoospermia and severe oligozoospermia. However, current testing is limited in its ability to identify a variety of genetic and epigenetic conditions that might be implicated in both idiopathic and unexplained infertility. Several epimutations of imprinting genes and developmental genes have been postulated to be candidate markers for male infertility. As such, development of novel diagnostic panels is essential to change the current landscape with regard to prevention, diagnosis and management. Understanding the underlying genetic mechanisms related to the pathophysiology of male infertility, and the impact of environmental exposures and lifestyle factors on gene expression might aid clinicians in developing individualised treatment strategies.
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Affiliation(s)
- Sezgin Gunes
- Medical Biology, Medical Faculty, Ondokuz Mayis University, Samsun, Turkey.,Molecular Medicine, Medical Faculty, Ondokuz Mayis University, Samsun, Turkey
| | - Sandro C Esteves
- ANDROFERT, Andrology and Human Reproduction Clinic, Referral Center for Male Reproduction, Campinas, São Paulo, SP, Brazil.,Department of Surgery (Division of Urology), University of Campinas (UNICAMP), Campinas, São Paulo, SP, Brazil.,Faculty of Health, Aarhus University, Aarhus, Denmark
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12
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Hajihoseini M, Mehrabani D, Vahdati A, Hosseini SE, Tamadon A, Dianatpour M, Rahmanifar F. Spermatogenesis after Transplantation of Adipose Tissue-Derived Stem Cells in Azoospermic Guinea Pigs: A Histological and Histomorphometric Study. Galen Med J 2018; 7:e1000. [PMID: 34466423 PMCID: PMC8343795 DOI: 10.22086/gmj.v0i0.1000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2017] [Revised: 09/20/2017] [Accepted: 11/17/2017] [Indexed: 11/30/2022] Open
Abstract
Background: The purpose of this research was to determine histomorphometric changes in busulfan-induced azoospermia after transplantation of Adipose Tissue-Derived Stem Cells (AdSCs) in guinea pig. AdSCs were isolated from adipose tissue around the testes of guinea pigs and characterized for mesenchymal properties. Materials and Methods: Guinea pigs were allocated into three groups, including the control group without any intervention. To induce azoospermia, groups 2 and 3 received a dose of 40 mg/kg of busulfan with 21 days interval. Group 3 received 1×106 AdSCs in their seminiferous tubules of left testes, 35 days following last busulfan injection, while right testis in the group was considered for comparison as controls. Sixty days following transplantation of cell, histomorphometric and histopathologic changes of the experiments were assessed. Results: After AdSCs’ transplantation, normal spermatogenesis appearance was noticed compared to busulfan-induced azoospermia and AdSCs recovered spermatogenesis, and our findings can be added to the literature in treating azoospermic infertilities. Conclusion: The transplanted AdSCs could induce production of germinal cells using testicular seminiferous tubules and were an effective source in treating azoospermia
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Affiliation(s)
- Mehrdokht Hajihoseini
- Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran.,Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
| | - Davood Mehrabani
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Akbar Vahdati
- Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran.,Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
| | - Seyed Ebrahim Hosseini
- Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran.,Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
| | - Amin Tamadon
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Mehdi Dianatpour
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Farhad Rahmanifar
- Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
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Mahabadi JA, Sabzalipour H, Bafrani HH, Gheibi Hayat SM, Nikzad H. Application of induced pluripotent stem cell and embryonic stem cell technology to the study of male infertility. J Cell Physiol 2018; 233:8441-8449. [PMID: 29870061 DOI: 10.1002/jcp.26757] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Accepted: 04/23/2018] [Indexed: 01/18/2023]
Abstract
Stem cells (SCs) are classes of undifferentiated biological cells existing only at the embryonic, fetal, and adult stages that can divide to produce specialized cell types during fetal development and remain in our bodies throughout life. The progression of regenerative and reproductive medicine owes the advancement of respective in vitro and in vivo biological science on the stem cell nature under appropriate conditions. The SCs are promising therapeutic tools to treat currently of infertility because of wide sources and high potency to differentiate. Nevertheless, no effective remedies are available to deal with severe infertility due to congenital or gonadotoxic stem cell deficiency in prepubertal childhood. Some recent solutions have been developed to address the severe fertility problems, including in vitro formation of germ cells from stem cells, induction of pluripotency from somatic cells, and production of patient-specific pluripotent stem cells. There is a possibility of fertility restoration using the in vitro formation of germ cells from somatic cells. Accordingly, the present review aimed at studying the literature published on the medical application of stem cells in reproductive concerns.
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Affiliation(s)
- Javad Amini Mahabadi
- Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamed Sabzalipour
- Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | | | - Seyed Mohammad Gheibi Hayat
- Student Research Committee, Department of Medical Biotechnology, Faculty Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Nikzad
- Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran
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14
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Cui Z, Agarwal A, da Silva BF, Sharma R, Sabanegh E. Evaluation of seminal plasma proteomics and relevance of FSH in identification of nonobstructive azoospermia: A preliminary study. Andrologia 2018. [PMID: 29528137 DOI: 10.1111/and.12999] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Nonobstructive azoospermia (NOA) patients present with high levels of serum FSH. At the protein level, the aetiology and pathways underlying different subtypes of NOA are unclear. The aim was to evaluate quantitatively differences in proteomic profiles of NOA patients presenting with normal serum FSH and normal testicular volume and high serum FSH and small testicular volume. The study comprised of 14 nonobstructive azoospermic men (N = 4; normal FSH and normal testicular volume and N = 10; high FSH and small testicular volume) and seven normozoospermic men. Proteomic analysis was done using LC-MS. GSTM3 and PGK2 were less abundant in the normal and high FSH group compared to controls. HSPA4L and HSPA4 were exclusively present in control group whereas HSP90AB1, HSPA1B, HSP90AA1 and HSPA2 were less abundant and exclusive to the normal and high FSH group. We have identified six heat-shock proteins that may have a role in the pathology of NOA. FSH and testicular volume by itself are not good markers of NOA. The inverse association of GSTM3 and PGK2 regulation with FSH levels along with 12 proteins exclusively in NOA groups suggests further evaluation of their predictive potential in a larger cohort of patients.
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Affiliation(s)
- Z Cui
- American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA.,Institute of Toxicology, Third Military Medical University, Chongqing, China
| | - A Agarwal
- American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - B F da Silva
- Human Reproduction Section, Division of Urology, Department of Surgery, São Paulo Federal University, São Paulo, Brazil
| | - R Sharma
- American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - E Sabanegh
- Department of Urology, Cleveland Clinic, Cleveland, OH, USA
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15
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Vahdati A, Fathi A, Hajihoseini M, Aliborzi G, Hosseini E. The Regenerative Effect of Bone Marrow-Derived Stem Cells in Spermatogenesis of Infertile Hamster. World J Plast Surg 2017; 6:18-25. [PMID: 28289609 PMCID: PMC5339605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Infertility is a serious social problem in advanced nations, with male factor in half of all cases of infertility. This study was conducted to determine the regenerative effect of bone marrow-derived stem cells in spermatogenesis of infertile hamster. METHODS Twelve adult male hamsters were equally divided into azoospermic and control groups. Busulfan was intraperitoneally used for induction of azoospermia, while the right testis was treated with bone marrow-derived stem cells (106 BM-SCs), labeled with sterile trypan blue, 35 days after busulfan injection. The left testis served as positive control for azoospermia. Sixty days after cell transplantation, the animals were euthanized and both testes were removed and evaluated histologically. RESULTS BM-SCs were spindle-shaped, adherent to the culture flasks and had positive expression of CD29 and CD73 and negative expression of CD45. Alcian blue staining confirmed differentiation of BM-SCs into chondrocytes. Karyotyping denoted to stability of chromosomes. Treatment with busulfan in seminiferous tubules resulted into distruption of spermatogenesis. After two months in busulfan treatment group, seminiferous tubular atrophy and germinal epitheliums degenerations were noticed with no spermatozoa in epididymis. After treatment of busulfan group with BM-SCs, spermatogonia, primary spermatocytes, spermatids and sperms were present in seminiferous tubules. CONCLUSION As cell transplantation in seminiferous tubules resulted into a rapid repair of pathological changes, BM-SCs can be recommended an effective treatment measure in azoospermia. It seems that more studies are necessary to confirm the use of this technique in treatment of azoospermia and infertility in human.
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Affiliation(s)
- Akbar Vahdati
- Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran;,Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran,Corresponding Author: Akbar Vahdati, PhD; Professor of Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran, Tel: +98-71-32341025,
| | - Alireza Fathi
- Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran;,Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
| | - Mehrdokht Hajihoseini
- Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran;,Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
| | - Ghaem Aliborzi
- Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran;,Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
| | - Ebrahim Hosseini
- Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran;,Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
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16
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Esteves SC. Novel concepts in male factor infertility: clinical and laboratory perspectives. J Assist Reprod Genet 2016; 33:1319-1335. [PMID: 27423664 PMCID: PMC5065546 DOI: 10.1007/s10815-016-0763-8] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Accepted: 06/22/2016] [Indexed: 12/22/2022] Open
Abstract
In recent years, the management of male factor infertility has undergone important changes with the introduction of novel concepts, advanced testing, and therapeutic interventions. This review highlights some of these changes and discusses their impact to routine clinical practice. First, we discuss the recent changes in the World Health Organization (WHO) laboratory methods and reference values for the examination of human semen. Second, we examine the role of sperm chromatin integrity tests in light of increasing evidence of the detrimental effect of sperm DNA fragmentation on reproductive outcomes. Third, we summarize the main findings of varicocele-related infertility and the outcomes of microsurgical varicocele repair to different case scenarios. Lastly, we critically discuss the current management of men with nonobstructive azoospermia seeking fertility and the new opportunities that emerged to help these men achieve biological fatherhood.
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Affiliation(s)
- Sandro C Esteves
- ANDROFERT, Andrology and Human Reproduction Clinic, Referral Center for Male Reproduction, Av. Dr. Heitor Penteado, 1464, Campinas, SP, 13075-460, Brazil.
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17
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Samanta L, Swain N, Ayaz A, Venugopal V, Agarwal A. Post-Translational Modifications in sperm Proteome: The Chemistry of Proteome diversifications in the Pathophysiology of male factor infertility. Biochim Biophys Acta Gen Subj 2016; 1860:1450-65. [DOI: 10.1016/j.bbagen.2016.04.001] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Revised: 03/26/2016] [Accepted: 04/04/2016] [Indexed: 12/18/2022]
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Abstract
The clinical management of men with nonobstructive azoospermia (NOA) seeking fertility has been a challenge for andrologists, urologists, and reproductive medicine specialists alike. This review presents a personal perspective on the clinical management of NOA, including the lessons learned over 15 years dealing with this male infertility condition. A five-consecutive-step algorithm is proposed to manage such patients. First, a differential diagnosis of azoospermia is made to confirm/establish that NOA is due to spermatogenic failure. Second, genetic testing is carried out not only to detect the males in whom NOA is caused by microdeletions of the long arm of the Y chromosome, but also to counsel the affected patients about their chances of having success in sperm retrieval. Third, it is determined whether any intervention prior to a surgical retrieval attempt may be used to increase sperm production. Fourth, the most effective and efficient retrieval method is selected to search for testicular sperm. Lastly, state-of-art laboratory techniques are applied in the handling of retrieved gametes and cultivating the embryos resulting from sperm injections. A coordinated multidisciplinary effort is key to offer the best possible chance of achieving a biological offspring to males with NOA.
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Affiliation(s)
- Sandro C Esteves
- ANDROFERT, Center for Male Reproduction, Campinas 13075-460, Brazil
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19
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Yu XJ, Dong L, Ren FQ, Chen DA, Zhang PH, Cai J, You YD, Li GS, Chang DG. Intracytoplasmic sperm injection (ICSI) outcomes of azoospermia with different causes: 107 cases report. Int J Clin Exp Med 2015; 8:21684-21688. [PMID: 26885126 PMCID: PMC4723971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Accepted: 11/11/2015] [Indexed: 06/05/2023]
Abstract
This retrospective analysis compared the outcomes of fertilization and pregnancy rates of 107 azoospermia patients treating with intracytoplasmic sperm injection (ICSI). Sperms were obtained by testicular biopsy surgery, with which we used in ICSI subsequently. The outcomes were compared by different kinds of causes leading to azoospermia in the 107 cases. 69 cases of obstructive azoospermia and 38 cases non-obstructive, the fertilization rates were 61.94% and 53.47% respectively, and pregnancy rates were 67.65% and 52.63%. 78 cases with normal volume testes and 29 cases with small testes, the fertilization rates were 70.93% and 48.80% respectively, and pregnancy rates were 66.25% and 50.00%. There was significant difference in fertilization rates between obstructive, non-obstructive and normal volume testes, small testes (P < 0.05), but no significant difference in pregnancy rates (P > 0.05). The pregnancy rate was significant difference between female age < 32 and ≥ 32 whatever the cause of azoospermia was (P < 0.05). Our study reveals that obstructive azoospermia and normal volume testes have higher fertilization rates in ICSI, but the pregnancy rates are only related to female age.
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Affiliation(s)
- Xu-Jun Yu
- Department of Andrology, The 2nd Teaching Hospital, Chengdu University of Traditional Chinese MedicineChengdu 610041, Sichuan, China
| | - Liang Dong
- Chengdu University of Traditional Chinese MedicineChengdu 610072, Sichuan, China
| | - Fei-Qiang Ren
- Chengdu University of Traditional Chinese MedicineChengdu 610072, Sichuan, China
| | - Di-Ang Chen
- Chengdu University of Traditional Chinese MedicineChengdu 610072, Sichuan, China
| | - Pei-Hai Zhang
- Department of Urology and Andrology, Sichuan Integrative Medicine HospitalChengdu 610041, Sichuan, China
| | - Jian Cai
- Department of Urology and Andrology, The 1st Teaching Hospital, Chengdu University of Traditional Chinese MedicineChengdu 610072, Sichuan, China
| | - Yao-Dong You
- Department of Urology and Andrology, The 1st Teaching Hospital, Chengdu University of Traditional Chinese MedicineChengdu 610072, Sichuan, China
| | - Guang-Sen Li
- Department of Urology and Andrology, The 1st Teaching Hospital, Chengdu University of Traditional Chinese MedicineChengdu 610072, Sichuan, China
| | - De-Gui Chang
- Department of Andrology, The 2nd Teaching Hospital, Chengdu University of Traditional Chinese MedicineChengdu 610041, Sichuan, China
- Department of Urology and Andrology, The 1st Teaching Hospital, Chengdu University of Traditional Chinese MedicineChengdu 610072, Sichuan, China
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20
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Ceylan GG, Ceylan C. Genetics and male infertility. World J Clin Urol 2015; 4:38-47. [DOI: 10.5410/wjcu.v4.i1.38] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Revised: 09/05/2014] [Accepted: 01/12/2015] [Indexed: 02/06/2023] Open
Abstract
The goal of this review is to explain the requirement for understanding the genetic structure of infertility arising from male factor and to discuss the essentials of these genetic elements (2). The majority of the population is affected by this disorder caused by male factor infertility (1); but the etiologies are still unknown. After the primary genetic structure in infertile phenotypes is searched, an evaluation can be made. Thus the reasons causing infertility can be discovered and patients can benefit from effective therapies (1). Publications about male infertility within the recent 10 years in the Pubmed database were discussed (1). There are some approachments for describing the function of specific genes, but no adequate study is present to be useful for diagnosing and treating male infertility (1). Male fertility and fertility in offspring of males are considerably affected by the exact transition of epigenetic information (1). When the genetic factors playing a role in male infertility were analysed, significant steps will be taken for treating patients and determining the reasons of idiopathic infertility (1). Developments in technology associated with the impact of genetics may enable to specify the etiology of male infertility by determining specific infertile phenotype marks (1).
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