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Saez Lancellotti TE, Avena MV, Funes AK, Bernal-López MR, Gómez-Huelgas R, Fornes MW. Exploring the impact of lipid stress on sperm cytoskeleton: insights and prospects. Nat Rev Urol 2025; 22:294-312. [PMID: 39528754 DOI: 10.1038/s41585-024-00952-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/02/2024] [Indexed: 11/16/2024]
Abstract
The decline in male fertility correlates with the global rise in obesity and dyslipidaemia, representing significant public health challenges. High-fat diets induce metabolic alterations, including hypercholesterolaemia, hepatic steatosis and atherosclerosis, with detrimental effects on testicular function. Testicular tissue, critically dependent on lipids for steroidogenesis, is particularly vulnerable to these metabolic disruptions. Excessive lipid accumulation within the testes, including cholesterol, triglycerides and specific fatty acids, disrupts essential sperm production processes such as membrane formation, maturation, energy metabolism and cell signalling. This leads to apoptosis, impaired spermatogenesis, and abnormal sperm morphology and function, ultimately compromising male fertility. During spermiogenesis, round spermatids undergo extensive reorganization, including the formation of the acrosome, manchette and specialized filamentous structures, which are essential for defining the final sperm cell shape. In this Perspective, we examine the impact of high-fat diets on the cytoskeleton of spermatogenic cells and its consequences to identify the mechanisms underlying male infertility associated with dyslipidaemia. Understanding these processes may facilitate the development of therapeutic strategies, such as dietary interventions or natural product supplementation, that aim to address infertility in men with obesity and hypercholesterolaemia. The investigation of cytoskeleton response to lipid stress extends beyond male reproduction, offering insights with broader implications.
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Affiliation(s)
- Tania E Saez Lancellotti
- Laboratorio de Biología Molecular del Metabolismo & Nutrición (MeNu), Instituto de Histología y Embriología (IHEM), Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina.
- Instituto de Investigaciones, Facultad de Ciencias Médicas, Universidad del Aconcagua, Mendoza, Argentina.
- Servicio de Medicina Interna, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain.
| | - María V Avena
- Laboratorio de Biología Molecular del Metabolismo & Nutrición (MeNu), Instituto de Histología y Embriología (IHEM), Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina
- Laboratorio de Investigaciones Andrológicas de Mendoza (LIAM), Instituto de Histología y Embriología (IHEM), CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina
| | - Abi K Funes
- Laboratorio de Biología Molecular del Metabolismo & Nutrición (MeNu), Instituto de Histología y Embriología (IHEM), Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina
- Laboratorio de Investigaciones Andrológicas de Mendoza (LIAM), Instituto de Histología y Embriología (IHEM), CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina
| | - María-Rosa Bernal-López
- Servicio de Medicina Interna, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
| | - Ricardo Gómez-Huelgas
- Servicio de Medicina Interna, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
| | - Miguel W Fornes
- Laboratorio de Investigaciones Andrológicas de Mendoza (LIAM), Instituto de Histología y Embriología (IHEM), CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina
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Sutovsky P, Zelenkova N, Postlerova P, Zigo M. Proteostasis as a Sentry for Sperm Quality and Male Fertility. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2025; 1469:273-303. [PMID: 40301261 DOI: 10.1007/978-3-031-82990-1_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/01/2025]
Abstract
In the last two decades, a school of thought emerged that perceives male reproductive health, testicular function, and sperm output as a sentry for general, somatic health. Large-scale epidemiologic studies have already linked the reduced sperm count to increased risk of chronic somatic disease (e.g., cancer, cardiovascular, neurological and bone diseases), yet most of these studies have not taken full advantage of advanced andrological analysis. Altered proteostasis, i.e., the disbalance between protein synthesis and turnover, is a common denominator of many diseases, including but not limited to cancer and neurodegenerative diseases. This chapter introduces the concept of cellular proteostasis as a measure of sperm structural and functional integrity and an endpoint of varied impacts on spermiogenesis and sperm maturation, including heritability, general health, lifestyle, and occupational and environmental reprotoxic exposure. Special consideration is given to small molecule protein modifiers, sperm-binding seminal plasma proteins, zinc-interacting proteins, and redox proteins responsible for the maintenance of protein structure and the protection of spermatozoa from oxidative damage. While the main focus is on human male infertility, serious consideration is given to relevant animal models, and in particular to male food animals with extensive records of fertility from artificial insemination services. Altogether, the proteostatic biomarker discovery and validation studies set the stage for the integration of proteomics of sperm proteostasis with genomic and high throughput phenomic approaches to benefit both human and animal reproductive medicine.
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Affiliation(s)
- Peter Sutovsky
- Division of Animal Sciences, University of Missouri, Columbia, MO, USA.
- Department of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, MO, USA.
| | - Natalie Zelenkova
- Division of Animal Sciences, University of Missouri, Columbia, MO, USA
- Department of Veterinary Sciences, Faculty of Agrobiology, Food, and Natural Resources, Czech University of Life Sciences, Prague, Czech Republic
| | - Pavla Postlerova
- Department of Veterinary Sciences, Faculty of Agrobiology, Food, and Natural Resources, Czech University of Life Sciences, Prague, Czech Republic
- Laboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Vestec, Czech Republic
| | - Michal Zigo
- Division of Animal Sciences, University of Missouri, Columbia, MO, USA
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Yuan S, Zhang Y, Dong PY, Chen Yan YM, Liu J, Zhang BQ, Chen MM, Zhang SE, Zhang XF. A comprehensive review on potential role of selenium, selenoproteins and selenium nanoparticles in male fertility. Heliyon 2024; 10:e34975. [PMID: 39144956 PMCID: PMC11320318 DOI: 10.1016/j.heliyon.2024.e34975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 07/17/2024] [Accepted: 07/19/2024] [Indexed: 08/16/2024] Open
Abstract
Selenium (Se), a component of selenoproteins and selenocompounds in the human body, is crucial for the development of male reproductive organs, DNA synthesis, thyroid hormone, metabolism, and defence against infections and oxidative damage. In the testis, it must exceed a desirable level since either a shortage or an overabundance causes aberrant growth. The antioxidant properties of selenium are essential for preserving human reproductive health. Selenoproteins, which have important structural and enzymatic properties, control the biological activities of Se primarily. These proteins specifically have a role in metabolism and a variety of cellular processes, such as the control of selenium transport, thyroid hormone metabolism, immunity, and redox balance. Selenium nanoparticles (SeNPs) are less hazardous than selenium-based inorganic and organic materials. Upon being functionalized with active targeting ligands, they are both biocompatible and capable of efficiently delivering combinations of payloads to particular cells. In this review, we discuss briefly the chemistry, structure and functions of selenium and milestones of selenium and selenoproteins. Next we discuss the various factors influences male infertility, biological functions of selenium and selenoproteins, and role of selenium and selenoproteins in spermatogenesis and male fertility. Furthermore, we discuss the molecular mechanism of selenium transport and protective effects of selenium on oxidative stress, apoptosis and inflammation. We also highlight critical contribution of selenium nanoparticles on male fertility and spermatogenesis. Finally ends with conclusion and future perspectives.
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Affiliation(s)
- Shuai Yuan
- College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, 266109, China
| | - Ye Zhang
- Advanced Medical Research Institute, Shandong University, Jinan, Shandong, 250014, China
| | - Pei-Yu Dong
- College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, 266109, China
| | - Yu-Mei Chen Yan
- College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, 266109, China
| | - Jing Liu
- Analytical & Testing Center of Qingdao Agricultural University, Qingdao, 266100, China
| | - Bing-Qiang Zhang
- Qingdao Restore Biotechnology Co., Ltd., Qingdao, 266111, China
- Key Laboratory of Cancer and Immune Cells of Qingdao, Qingdao, 266111, China
| | - Meng-Meng Chen
- Qingdao Restore Biotechnology Co., Ltd., Qingdao, 266111, China
- Key Laboratory of Cancer and Immune Cells of Qingdao, Qingdao, 266111, China
| | - Shu-Er Zhang
- Animal Husbandry General Station of Shandong Province, Jinan, 250010, China
| | - Xi-Feng Zhang
- College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, 266109, China
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Netherton JK, Ogle RA, Robinson BR, Molloy M, Krisp C, Velkov T, Casagranda F, Dominado N, Silva Balbin Villaverde AI, Zhang XD, Hime GR, Baker MA. The role of HnrnpF/H as a driver of oligoteratozoospermia. iScience 2024; 27:110198. [PMID: 39092172 PMCID: PMC11292545 DOI: 10.1016/j.isci.2024.110198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 02/20/2024] [Accepted: 06/03/2024] [Indexed: 08/04/2024] Open
Abstract
Male subfertility or infertility is a common condition often characterized by men producing a low number of sperm with poor quality. To gain insight into this condition, we performed a quantitative proteomic analysis of semen samples obtained from infertile and fertile men. At least 6 proteins showed significant differences in regulation of alternatively spliced isoforms. To investigate this link between aberrant alternative splicing and production of poor-quality spermatozoa, we overexpressed the hnrnpH/F-orthologue Glorund (Glo) in Drosophila, which was also found to be abundant in poor quality human sperm. Transgenic animals produced low numbers of morphologically defective spermatozoa and aberrant formation of the "dense body," an organelle akin to the mammalian manchette. Furthermore, fertility trials demonstrated that transgenic flies were either completely infertile or highly subfertile. These findings suggest that dysregulation of hnrnpH/F is likely to result in the production of low-quality semen, leading to subfertility or infertility in men.
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Affiliation(s)
- Jacob K. Netherton
- School of Biomedical Sciences and Pharmacy, Faculty of Medicine and Health, University of Newcastle, Callaghan, NSW 2308, Australia
| | - Rachel A. Ogle
- School of Biomedical Sciences and Pharmacy, Faculty of Medicine and Health, University of Newcastle, Callaghan, NSW 2308, Australia
| | - Benjamin R. Robinson
- School of Biomedical Sciences and Pharmacy, Faculty of Medicine and Health, University of Newcastle, Callaghan, NSW 2308, Australia
| | - Mark Molloy
- Australian Proteome Analysis Facility, Department of Biomolecular Sciences, Macquarie University, NSW 2109 Australia
| | - Christoph Krisp
- Australian Proteome Analysis Facility, Department of Biomolecular Sciences, Macquarie University, NSW 2109 Australia
| | - Tony Velkov
- Biomedicine Discovery Institute, Infection & Immunity Program and Department of Microbiology, Monash University, Clayton, VIC 3168, Australia
| | - Franca Casagranda
- Department of Anatomy and Physiology, University of Melbourne, Parkville, VIC 3010, Australia
| | - Nicole Dominado
- Department of Anatomy and Physiology, University of Melbourne, Parkville, VIC 3010, Australia
| | | | - Xu Dong Zhang
- School of Biomedical Sciences and Pharmacy, Faculty of Medicine and Health, University of Newcastle, Callaghan, NSW 2308, Australia
| | - Gary R. Hime
- Department of Anatomy and Physiology, University of Melbourne, Parkville, VIC 3010, Australia
| | - Mark A. Baker
- School of Biomedical Sciences and Pharmacy, Faculty of Medicine and Health, University of Newcastle, Callaghan, NSW 2308, Australia
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Alfaiate MI, Tavares RS, Ramalho-Santos J. A ripple effect? The impact of obesity on sperm quality and function. Reprod Fertil Dev 2024; 36:RD23215. [PMID: 38589340 DOI: 10.1071/rd23215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 03/15/2024] [Indexed: 04/10/2024] Open
Abstract
Infertility affects approximately 15% of couples trying to conceive. Male-related causes account for roughly 50% of cases, with obesity emerging as a possible significant factor. Obesity, defined as a body mass index of 30.0 or higher, has become a widespread epidemic associated with numerous health issues, including a decrease of fertility. This review discusses the relationship between obesity and male infertility, particularly focusing on sperm quality and function. An overview of the literature suggests that obesity may influence the male reproductive system via disruptions in hormonal profiles, oxidative stress, and inflammation, leading to changes in sperm parameters. Several studies have discussed if obesity causes a decrease in sperm concentration, motility, and normal morphology, so far without a consensus being reached. However, available evidence suggests an impairment of sperm function in obese men, due to an increase in DNA damage and oxidative stress, impaired mitochondrial function and acrosome reaction in response to progesterone. Finally, the relationship between obesity and assisted reproductive technologies outcomes remains debatable, with conflicting evidence regarding the influence on fertilisation, pregnancy, and live birth rates. Therefore, the actual impact of obesity on human spermatozoa still needs to be clarified, due to the multiple factors potentially in play.
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Affiliation(s)
- Maria Inês Alfaiate
- University of Coimbra, CNC-UC, Center for Neuroscience and Cell Biology, CIBB, Coimbra, Portugal; and University of Coimbra, Institute for Interdisciplinary Research, Doctoral Programme in Experimental Biology and Biomedicine (PDBEB), Coimbra, Portugal
| | - Renata Santos Tavares
- University of Coimbra, CNC-UC, Center for Neuroscience and Cell Biology, CIBB, Coimbra, Portugal; and Department of Life Sciences, University of Coimbra, Coimbra 3000-456, Portugal
| | - João Ramalho-Santos
- University of Coimbra, CNC-UC, Center for Neuroscience and Cell Biology, CIBB, Coimbra, Portugal; and Department of Life Sciences, University of Coimbra, Coimbra 3000-456, Portugal
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Sciorio R, Tramontano L, Adel M, Fleming S. Decrease in Sperm Parameters in the 21st Century: Obesity, Lifestyle, or Environmental Factors? An Updated Narrative Review. J Pers Med 2024; 14:198. [PMID: 38392631 PMCID: PMC10890002 DOI: 10.3390/jpm14020198] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 02/05/2024] [Accepted: 02/08/2024] [Indexed: 02/24/2024] Open
Abstract
Semen quality represents a compelling factor for fertility, and delineating the normal values has proven difficult. In the last four decades, several authors have reported a noticeable decline in sperm parameters. Also, studies investigating 'time to pregnancy' have shown that fecundity begins to be reduced when sperm numbers decrease below 30 million, even though according to the 6th edition of the WHO manual, the normal value is currently 16 million/mL or 39 million per ejaculate. There exists sufficient data to suggest a decline in sperm counts over time, even though the clear reason for this adverse trend is not well established, but some associations have been hypothesised, such as maternal smoking during pregnancy. Additional potential factors have yet to be fully illustrated but involve poor diet, increased obesity, and exposure to environmental toxins. Moreover, the change in environmental conditions and more common exposure to endocrine-disrupting chemicals (EDCs), such as pesticides and herbicides, as well as bisphenol A, phthalates, polychlorinated biphenyls, and heavy metals, starting from prenatal life and continuing into adulthood, may exhibit probable features explaining the reduction in sperm parameters. Therefore, the main goal of this narrative review is to furnish an overview of the possible effects of exposure to EDCs on testicular function and spermatogenesis and, also, to summarise the evidence regarding a decrease in sperm quality and examine its potential consequences.
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Affiliation(s)
- Romualdo Sciorio
- Fertility Medicine and Gynaecological Endocrinology Unit, Department Woman-Mother-Child, Lausanne University Hospital, 1011 Lausanne, Switzerland
| | - Luca Tramontano
- Department of Women, Infants and Adolescents, Division of Obstetrics, Geneva University Hospitals, 1211 Geneve, Switzerland
| | - Mohammed Adel
- Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11651, Egypt
| | - Steven Fleming
- Discipline of Anatomy & Histology, School of Medical Sciences, University of Sydney, Sydney, NSW 2006, Australia
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Corda PO, Moreira J, Howl J, Oliveira PF, Fardilha M, Silva JV. Differential Proteomic Analysis of Human Sperm: A Systematic Review to Identify Candidate Targets to Monitor Sperm Quality. World J Mens Health 2024; 42:71-91. [PMID: 37118964 PMCID: PMC10782124 DOI: 10.5534/wjmh.220262] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 01/24/2023] [Accepted: 02/05/2023] [Indexed: 04/30/2023] Open
Abstract
PURPOSE The advent of proteomics provides new opportunities to investigate the molecular mechanisms underlying male infertility. The selection of relevant targets based on a single analysis is not always feasible, due to the growing number of proteomic studies with conflicting results. Thus, this study aimed to systematically review investigations comparing the sperm proteome of normozoospermic and infertile men to define a panel of proteins with the potential to be used to evaluate sperm quality. MATERIALS AND METHODS A literature search was conducted on PubMed, Web of Science, and Scopus databases following the PRISMA guidelines. To identify proteins systematically reported, first the studies were divided by condition into four groups (asthenozoospermia, low motility, unexplained infertility, and infertility related to risk factors) and then, all studies were analysed simultaneously (poor sperm quality). To gain molecular insights regarding identified proteins, additional searches were performed within the Human Protein Atlas, Mouse Genome Informatics, UniProt, and PubMed databases. RESULTS Thirty-two studies were included and divided into 4 sub-analysis groups. A total of 2752 proteins were collected, of which 38, 1, 3 and 2 were indicated as potential markers for asthenozoospermia, low motility, unexplained infertility and infertility related to risk factors, respectively, and 58 for poor sperm quality. Among the identified proteins, ACR, ACRBP, ACRV1, ACTL9, AKAP4, ATG3, CCT2, CFAP276, CFAP52, FAM209A, GGH, HPRT1, LYZL4, PRDX6, PRSS37, REEP6, ROPN1B, SPACA3, SOD1, SPEM1, SPESP1, SPINK2, TEKT5, and ZPBP were highlighted due to their roles in male reproductive tissues, association with infertility phenotypes or participation in specific biological functions in spermatozoa. CONCLUSIONS Sperm proteomics allows the identification of protein markers with the potential to overcome limitations in male infertility diagnosis and to understand changes in sperm function at the molecular level. This study provides a reliable list of systematically reported proteins that could be potential targets for further basic and clinical studies.
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Affiliation(s)
- Pedro O Corda
- Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
| | - Jéssica Moreira
- Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
| | - John Howl
- Research Institute in Healthcare Science, University of Wolverhampton, Wolverhampton, UK
| | - Pedro F Oliveira
- LAQV/REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, Portugal
| | - Margarida Fardilha
- Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal.
| | - Joana Vieira Silva
- Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
- LAQV/REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, Portugal
- Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal
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Castillo J, de la Iglesia A, Leiva M, Jodar M, Oliva R. Proteomics of human spermatozoa. Hum Reprod 2023; 38:2312-2320. [PMID: 37632247 DOI: 10.1093/humrep/dead170] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 07/12/2023] [Indexed: 08/27/2023] Open
Abstract
Proteomic methodologies offer a robust approach to identify and quantify thousands of proteins from semen components in both fertile donors and infertile patients. These strategies provide an unprecedented discovery potential, which many research teams are currently exploiting. However, it is essential to follow a suitable experimental design to generate robust data, including proper purification of samples, appropriate technical procedures to increase identification throughput, and data analysis following quality criteria. More than 6000 proteins have been described so far through proteomic analyses in the mature sperm cell, increasing our knowledge on processes involved in sperm function, intercommunication between spermatozoa and seminal fluid, and the transcriptional origin of the proteins. These data have been complemented with comparative studies to ascertain the potential role of the identified proteins on sperm maturation and functionality, and its impact on infertility. By comparing sperm protein profiles, many proteins involved in the acquisition of fertilizing ability have been identified. Furthermore, altered abundance of specific protein groups has been observed in a wide range of infertile phenotypes, including asthenozoospermia, oligozoospermia, and normozoospermia with unsuccessful assisted reproductive techniques outcomes, leading to the identification of potential clinically useful protein biomarkers. Finally, proteomics has been used to evaluate alterations derived from semen sample processing, which might have an impact on fertility treatments. However, the intrinsic heterogeneity and inter-individual variability of the semen samples have resulted in a relatively low overlap among proteomic reports, highlighting the relevance of combining strategies for data validation and applying strict criteria for proteomic data analysis to obtain reliable results. This mini-review provides an overview of the most critical steps to conduct robust sperm proteomic studies, the most relevant results obtained so far, and potential next steps to increase the impact of sperm proteomic data.
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Affiliation(s)
- Judit Castillo
- Molecular Biology of Reproduction and Development Research Group, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Fundació Clínic per a la Recerca Biomèdica, Universitat de Barcelona (UB), Barcelona, Spain
| | - Alberto de la Iglesia
- Molecular Biology of Reproduction and Development Research Group, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Fundació Clínic per a la Recerca Biomèdica, Universitat de Barcelona (UB), Barcelona, Spain
| | - Marina Leiva
- Molecular Biology of Reproduction and Development Research Group, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Fundació Clínic per a la Recerca Biomèdica, Universitat de Barcelona (UB), Barcelona, Spain
| | - Meritxell Jodar
- Molecular Biology of Reproduction and Development Research Group, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Fundació Clínic per a la Recerca Biomèdica, Universitat de Barcelona (UB), Barcelona, Spain
- Biochemistry and Molecular Genetics Service, Biomedical Diagnostic Center (CDB), Hospital Clínic de Barcelona, Barcelona, Spain
| | - Rafael Oliva
- Molecular Biology of Reproduction and Development Research Group, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Fundació Clínic per a la Recerca Biomèdica, Universitat de Barcelona (UB), Barcelona, Spain
- Biochemistry and Molecular Genetics Service, Biomedical Diagnostic Center (CDB), Hospital Clínic de Barcelona, Barcelona, Spain
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9
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Hodge MJ, de Las Heras-Saldana S, Rindfleish SJ, Stephen CP, Pant SD. QTLs and Candidate Genes Associated with Semen Traits in Merino Sheep. Animals (Basel) 2023; 13:2286. [PMID: 37508063 PMCID: PMC10376747 DOI: 10.3390/ani13142286] [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: 06/03/2023] [Revised: 07/06/2023] [Accepted: 07/07/2023] [Indexed: 07/30/2023] Open
Abstract
Ram semen traits play a significant role in conception outcomes, which in turn may influence reproductive efficiency and the overall productivity and profitability of sheep enterprises. Since hundreds of ewes may be inseminated from a single ejaculate, it is important to evaluate semen quality prior to use in sheep breeding programs. Given that semen traits have been found to be heritable, genetic variation likely contributes to the variability observed in these traits. Identifying such genetic variants could provide novel insights into the molecular mechanisms underlying variability in semen traits. Therefore, this study aimed to identify quantitative trait loci (QTLs) associated with semen traits in Merino sheep. A genome-wide association study (GWAS) was undertaken using 4506 semen collection records from 246 Merino rams collected between January 2002 and May 2021. The R package RepeatABEL was used to perform a GWAS for semen volume, gross motility, concentration, and percent post-thaw motility. A total of 35 QTLs, located on 16 Ovis aries autosomes (OARs), were significantly associated with either of the four semen traits in this study. A total of 89, 95, 33, and 73 candidate genes were identified, via modified Bonferroni, within the QTLs significantly associated with volume, gross motility, concentration, and percent post-thaw motility, respectively. Among the candidate genes identified, SORD, SH2B1, and NT5E have been previously described to significantly influence spermatogenesis, spermatozoal motility, and high percent post-thaw motility, respectively. Several candidate genes identified could potentially influence ram semen traits based on existing evidence in the literature. As such, validation of these putative candidates may offer the potential to develop future strategies to improve sheep reproductive efficiency. Furthermore, Merino ram semen traits are lowly heritable (0.071-0.139), and thus may be improved by selective breeding.
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Affiliation(s)
- Marnie J Hodge
- School of Agricultural, Environmental and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia
- Apiam Animal Health, Apiam Genetic Services, Dubbo, NSW 2830, Australia
| | - Sara de Las Heras-Saldana
- Animal Genetics and Breeding Unit, a Joint Venture of NSW Department of Primary Industries and University of New England, Armidale, NSW 2351, Australia
| | | | - Cyril P Stephen
- School of Agricultural, Environmental and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia
- Gulbali Institute, Charles Sturt University, Boorooma Street, Wagga Wagga, NSW 2678, Australia
| | - Sameer D Pant
- School of Agricultural, Environmental and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia
- Gulbali Institute, Charles Sturt University, Boorooma Street, Wagga Wagga, NSW 2678, Australia
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10
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Miyazaki MA, Guilharducci RL, Intasqui P, Bertolla RP. Mapping the human sperm proteome - novel insights into reproductive research. Expert Rev Proteomics 2023; 20:19-45. [PMID: 37140161 DOI: 10.1080/14789450.2023.2210764] [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: 05/05/2023]
Abstract
INTRODUCTION Spermatozoa are highly specialized cells with unique morphology. In addition, spermatozoa lose a considerable amount of cytoplasm during spermiogenesis, when they also compact their DNA, resulting in a transcriptionally quiescent cell. Throughout the male reproductive tract, sperm will acquire proteins that enable them to interact with the female reproductive tract. After ejaculation, proteins undergo post-translational modifications for sperm to capacitate, hyperactivate and fertilize the oocyte. Many proteins have been identified as predictors of male infertility, and also investigated in diseases that compromise reproductive potential. AREAS COVERED In this review we proposed to summarize the recent findings about the sperm proteome and how they affect sperm structure, function, and fertility. A literature search was performed using PubMed and Google Scholar databases within the past 5 years until August 2022. EXPERT OPINION Sperm function depends on protein abundance, conformation, and PTMs; understanding the sperm proteome may help to identify pathways essential to fertility, even making it possible to unravel the mechanisms involved in idiopathic infertility. In addition, proteomics evaluation offers knowledge regarding alterations that compromise the male reproductive potential.
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Affiliation(s)
- Mika Alexia Miyazaki
- Department of Surgery, Division of Urology, Human Reproduction Section, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Raquel Lozano Guilharducci
- Department of Surgery, Division of Urology, Human Reproduction Section, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Paula Intasqui
- Department of Surgery, Division of Urology, Human Reproduction Section, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Ricardo Pimenta Bertolla
- Department of Surgery, Division of Urology, Human Reproduction Section, Universidade Federal de São Paulo, São Paulo, Brazil
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11
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Li Y, Zhao W, Fu R, Ma Z, Hu Y, Liu Y, Ding Z. Endoplasmic reticulum stress increases exosome biogenesis and packaging relevant to sperm maturation in response to oxidative stress in obese mice. Reprod Biol Endocrinol 2022; 20:161. [PMID: 36411474 PMCID: PMC9677646 DOI: 10.1186/s12958-022-01031-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 11/03/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Mammalian sperm maturation in the epididymis is mainly modulated by exosomes that are secreted into the epididymal lumen from epididymal epithelial cells (EECs). Exposure to oxidative stress (OS) resulting from being fed a high fat diet (HFD) reduces sperm fertility, which is one of the cause inducing male infertility. Thus, we hypothesize that stress-induced changes in exosome content play a critical role in mediating this detrimental process. METHODS: An obese mouse model was established by feeding a HFD. Then oxidative stress status was measured in the mouse caput epididymis, epididymal fluid and spermatozoa. Meanwhile, epididymis-derived purified exosomes were isolated and validated. Subsequently, liquid chromatography tandem mass spectrometry (LC-MS) was used to perform proteomic analysis of purified exosomes. Gene Ontology (GO) analysis was performed along with pathway enrichment to identify differentially expressed proteins (DEPs). RESULTS Two hundred and two DEPs mostly related to endoplasmic reticulum (ER) function were identified in the exosomes separated from the epididymis of control mice and obese mice. The ER stress and CD63 (an exosome marker), both increased in the caput epididymis of obese mice. Furthermore, an in vitro study showed that palmitic acid (PA), an-oxidative stress inducer, increased exosome biogenesis and secretion in the EECs. CONCLUSION Oxidative stress in the epididymal microenvironment induces ER stress in the EECs. This effect alters the epididymis-derived exosome content, profile and amounts of their differentially expressed ER proteins. Such changes may affect exosome biogenesis and cargo packaging, finally leading to abnormalities in sperm maturation and fertility.
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Affiliation(s)
- Yangyang Li
- Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China
| | - Wenzhen Zhao
- Department of Histology and Embryology, School of Basic Medical Science, Dali University, 671000, Dali, Yunnan, China
| | - Rong Fu
- Department of Core Facility of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China
| | - Zhuoyao Ma
- Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China
| | - Yanqin Hu
- Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China
| | - Yue Liu
- Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.
| | - Zhide Ding
- Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.
- Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Jiao Tong University School of Medicine, No.280, Chongqing Road (South), 200025, Shanghai, China.
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12
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Lv JL, Wu QJ, Wang XB, Du Q, Liu FH, Guo RH, Leng X, Pan BC, Zhao YH. Intake of ultra-processed foods and asthenozoospermia odds: A hospital-based case-control study. Front Nutr 2022; 9:941745. [PMID: 36337657 PMCID: PMC9630735 DOI: 10.3389/fnut.2022.941745] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 09/28/2022] [Indexed: 11/17/2022] Open
Abstract
Background The intake of ultra-processed foods (UPFs) has increased rapidly in recent years. Evidence has suggested that UPFs has adverse effects on several health outcomes. This study aimed to first evaluate the association between the intake of UPFs and asthenozoospermia odds. Methods A hospital-based case-control study including 549 cases and 581 controls was performed in the infertility clinics of Shengjing Hospital of China Medical University from June 2020 to December 2020. Dietary intake was assessed using a validated food frequency questionnaire. Food items were categorized by the NOVA classification system based on the degree of processing. Semen parameters were analyzed according to the World Health Organization guidelines. Results The highest tertile of UPFs intake (% of total energy intake) was positively associated with the odds of asthenozoospermia (odds ratio [OR] = 1.53; 95% confidence interval [CI]: 1.12, 2.10; P for trend < 0.05), compared with the lowest tertile. Similar patterns were also found in subgroup analyses among participants with age ≥32 years (OR = 1.58; 95% CI: 1.04, 2.40), BMI ≥ 24 kg/m2 (OR = 1.52; 95% CI: 1.04, 2.22), ever cigarette smoking (OR = 1.78; 95% CI: 1.14, 2.79), and ever alcohol drinking (OR = 1.65; 95% CI: 1.01, 2.72), and in sensitivity analyses by using absolute amount (g/day) to calculate the intake of UPFs. Conclusion Higher consumption of UPFs was positively associated with the odds of asthenozoospermia. More studies are needed to confirm our findings.
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Affiliation(s)
- Jia-Le Lv
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qi-Jun Wu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiao-Bin Wang
- Center of Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qiang Du
- Center of Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Fang-Hua Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ren-Hao Guo
- Center of Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xu Leng
- Center of Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Bo-Chen Pan
- Center of Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
- *Correspondence: Bo-Chen Pan
| | - Yu-Hong Zhao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
- Yu-Hong Zhao
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13
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Huang Y, Li X, Sun X, Yao J, Gao F, Wang Z, Hu J, Wang Z, Ouyang B, Tu X, Zou X, Liu W, Lu M, Deng C, Yang Q, Xie Y. Anatomical Transcriptome Atlas of the Male Mouse Reproductive System During Aging. Front Cell Dev Biol 2022; 9:782824. [PMID: 35211476 PMCID: PMC8861499 DOI: 10.3389/fcell.2021.782824] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 12/28/2021] [Indexed: 11/13/2022] Open
Abstract
The elderly males undergo degenerative fertility and testicular endocrine function that jeopardize the reproductive health and well-being. However, the mechanisms underlying reproductive aging are unclear. Here, we tried to address this by investigating the phenotypes and transcriptomes of seven regions of the male mouse reproductive tract: the testis, efferent ductules, initial segment, caput, corpus and cauda epididymidis, and vas deferens, in adult (3 months) and aged (21 months) mice. Quantitative PCR, immunohistochemistry, immunofluorescent staining, and enzyme-linked immunosorbent assay were performed for the analysis of gene expression in mice, human tissues, and semen samples. Aged male mice showed both systematic and reproductive changes, and remarkable histological changes were detected in the testis and proximal epididymis. Transcriptomes of the male reproductive tract were mapped, and a series of region-specific genes were identified and validated in mouse and/or human tissues, including Protamine 1 (Prm2), ADAM metallopeptidase domain 28 (Adam28), Ribonuclease A family member 13 (Rnase13), WAP four-disulfide core domain 13 (Wfdc13), and Wfdc9. Meanwhile, age-related transcriptome changes of different regions of the male reproductive tract were characterized. Notably, increased immune response was functionally related to the male reproductive aging, especially the T cell activation. An immune response-associated factor, phospholipase A2 group IID (Pla2g2d), was identified as a potential biomarker for reproductive aging in mice. And the PLA2G2D level in human seminal plasma surged at approximately 35 years of age. Furthermore, we highlighted Protein tyrosine phosphatase receptor type C (Ptprc), Lymphocyte protein tyrosine kinase (Lck), Microtubule associated protein tau (Mapt), and Interferon induced protein with tetratricopeptide repeats 3 (Ifit3) as critical molecules in the aging of initial segment, caput, caput, and cauda epididymidis, respectively. This study provides an RNA-seq resource for the male reproductive system during aging in mice, and is expected to improve our understanding of male reproductive aging and infertility.
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Affiliation(s)
- Yanping Huang
- Department of Urology and Andrology, Renji Hospital, School of Medicine, Shanghai Institute of Andrology, Shanghai Jiao Tong University, Shanghai, China
| | - Xiangping Li
- Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiangzhou Sun
- Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jiahui Yao
- Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Fengxin Gao
- Guangzhou Epibiotek Co., Ltd., Guangzhou, China
| | - Zhenqing Wang
- Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jiaying Hu
- Department of Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Zhu Wang
- Department of Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Bin Ouyang
- Department of Andrology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Xiangan Tu
- Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xuenong Zou
- Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wei Liu
- Department of Urology and Andrology, Renji Hospital, School of Medicine, Shanghai Institute of Andrology, Shanghai Jiao Tong University, Shanghai, China
| | - Mujun Lu
- Department of Urology and Andrology, Renji Hospital, School of Medicine, Shanghai Institute of Andrology, Shanghai Jiao Tong University, Shanghai, China
| | - Chunhua Deng
- Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qiyun Yang
- Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yun Xie
- Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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14
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Corda PO, Silva JV, Pereira SC, Barros A, Alves MG, Fardilha M. Bioinformatic Approach to Unveil Key Differentially Expressed Proteins in Human Sperm After Slow and Rapid Cryopreservation. Front Cell Dev Biol 2022; 9:759354. [PMID: 35145967 PMCID: PMC8821918 DOI: 10.3389/fcell.2021.759354] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 12/23/2021] [Indexed: 11/25/2022] Open
Abstract
Currently, two conventional freezing techniques are used in sperm cryopreservation: slow freezing (SF) and rapid freezing (RF). Despite the protocolar improvements, cryopreservation still induces significant alterations in spermatozoon that are poorly understood. Here, available proteomic data from human cryopreserved sperm was analyzed through bioinformatic tools to unveil key differentially expressed proteins (DEPs) that can be used as modulation targets or quality markers. From the included proteomic studies, 160 and 555 DEPs were collected for SF and RF groups, respectively. For each group, an integrative network was constructed using gene ontology and protein-protein interaction data to identify key DEPs. Among them, arylsulfatase A (ARSA) was highlighted in both freezing networks, and low ARSA levels have been associated with poor-sperm quality. Thus, ARSA was selected for further experimental investigation and its levels were assessed in cryopreserved samples by western blot. ARSA levels were significantly decreased in RF and SF samples (∼31.97 and ∼39.28%, respectively). The bioinformatic analysis also revealed that the DEPs were strongly associated with proteasomal and translation pathways. The purposed bioinformatic approach allowed the identification of potential key DEPs in freeze-thawed human spermatozoa. ARSA has the potential to be used as a marker to assess sperm quality after cryopreservation.
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Affiliation(s)
- Pedro O Corda
- Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal
| | - Joana Vieira Silva
- Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal.,Department of Chemistry, QOPNA and LAQV, University of Aveiro, Aveiro, Portugal.,Clinical and Experimental Endocrinology, Department of Anatomy and Unit for Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
| | - Sara C Pereira
- Clinical and Experimental Endocrinology, Department of Anatomy and Unit for Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
| | - Alberto Barros
- Department of Chemistry, QOPNA and LAQV, University of Aveiro, Aveiro, Portugal.,Centre for Reproductive Genetics A. Barros, Porto, Portugal.,Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Marco G Alves
- Clinical and Experimental Endocrinology, Department of Anatomy and Unit for Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
| | - Margarida Fardilha
- Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal
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15
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Bisconti M, Simon JF, Grassi S, Leroy B, Martinet B, Arcolia V, Isachenko V, Hennebert E. Influence of Risk Factors for Male Infertility on Sperm Protein Composition. Int J Mol Sci 2021; 22:13164. [PMID: 34884971 PMCID: PMC8658491 DOI: 10.3390/ijms222313164] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 11/25/2021] [Accepted: 11/30/2021] [Indexed: 12/22/2022] Open
Abstract
Male infertility is a common health problem that can be influenced by a host of lifestyle risk factors such as environment, nutrition, smoking, stress, and endocrine disruptors. These effects have been largely demonstrated on sperm parameters (e.g., motility, numeration, vitality, DNA integrity). In addition, several studies showed the deregulation of sperm proteins in relation to some of these factors. This review inventories the literature related to the identification of sperm proteins showing abundance variations in response to the four risk factors for male infertility that are the most investigated in this context: obesity, diabetes, tobacco smoking, and exposure to bisphenol-A (BPA). First, we provide an overview of the techniques used to identify deregulated proteins. Then, we summarise the main results obtained in the different studies and provide a compiled list of deregulated proteins in relation to each risk factor. Gene ontology analysis of these deregulated proteins shows that oxidative stress and immune and inflammatory responses are common mechanisms involved in sperm alterations encountered in relation to the risk factors.
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Affiliation(s)
- Marie Bisconti
- Laboratory of Cell Biology, Research Institute for Biosciences, University of Mons, Place du Parc 20, 7000 Mons, Belgium; (M.B.); (S.G.); (E.H.)
| | - Jean-François Simon
- Fertility Clinic, CHU Ambroise Paré Hospital, Boulevard Kennedy 2, 7000 Mons, Belgium; (J.-F.S.); (V.A.)
| | - Sarah Grassi
- Laboratory of Cell Biology, Research Institute for Biosciences, University of Mons, Place du Parc 20, 7000 Mons, Belgium; (M.B.); (S.G.); (E.H.)
| | - Baptiste Leroy
- Laboratory of Proteomics and Microbiology, CISMa, Research Institute for Biosciences, University of Mons, 7000 Mons, Belgium;
| | - Baptiste Martinet
- Evolutionary Biology & Ecology, Université Libre de Bruxelles, Avenue Paul Héger, CP 160/12, 1000 Brussels, Belgium;
| | - Vanessa Arcolia
- Fertility Clinic, CHU Ambroise Paré Hospital, Boulevard Kennedy 2, 7000 Mons, Belgium; (J.-F.S.); (V.A.)
| | - Vladimir Isachenko
- Department of Obstetrics and Gynecology, University of Cologne, Kerpener Strasse 34, 50931 Cologne, Germany
| | - Elise Hennebert
- Laboratory of Cell Biology, Research Institute for Biosciences, University of Mons, Place du Parc 20, 7000 Mons, Belgium; (M.B.); (S.G.); (E.H.)
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16
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Wang XB, Wu QJ, Liu FH, Zhang S, Wang HY, Guo RH, Leng X, Du Q, Zhao YH, Pan BC. The Association Between Dairy Product Consumption and Asthenozoospermia Risk: A Hospital-Based Case-Control Study. Front Nutr 2021; 8:714291. [PMID: 34746202 PMCID: PMC8566545 DOI: 10.3389/fnut.2021.714291] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 09/21/2021] [Indexed: 12/26/2022] Open
Abstract
Background: Evidence of an association between dairy product and main related dairy nutrient intake, and the asthenozoospermia risk have been limited and controversial. Methods: A hospital-based case-control study including 549 men with asthenozoospermia and 581 normozoospermic controls was carried out in the infertility clinics of Shengjing Hospital of China Medical University between June, 2020 and December, 2020. Dietary intake was assessed with a validated food frequency questionnaire. According to the World Health Organization guidelines, semen parameters were collected through masturbation and were measured with WLJY9000 instrument and flow cytometry. The daily intake of dairy products and related nutrients was categorized into three groups according to control distribution, and the lowest tertile was used as the reference category. An unconditional multiple logistic regression was used to estimate the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for asthenozoospermia risk. Results: After adjustment for potential confounders, we found no statistically significant associations between the intake of total dairy products and asthenozoospermia risk (ORT3vs.T1 = 1.19, 95%CI = 0.85-1.67). Additionally, we generated null findings regarding the main related nutrients from dairy, including protein (ORT3vs.T1 = 1.19, 95%CI = 0.85-1.68), fat (ORT3vs.T1 = 1.28, 95%CI = 0.91-1.80), calcium (ORT3vs.T1 = 1.20, 95%CI = 0.85-1.68), saturated fatty acids (ORT3vs.T1 = 1.30, 95%CI = 0.92-1.83), and phosphorous (ORT3vs.T1 = 1.18, 95%CI = 0.84-1.67), and the asthenozoospermia risk. Of note, after stratification by body mass index (BMI), and the saturated fatty acids consumption from dairy was significantly associated with a higher asthenozoospermia risk (ORT3vs.T1 = 1.76, 95%CI = 1.01-3.09) among participants with a BMI below 25 kg/m2. Conclusion: This study provided limited evidence of an association between the intake of total dairy products and the main related dairy nutrients including protein, fat, calcium, saturated fatty acids, and phosphorus, and the asthenozoospermia risk. Further studies are warranted to confirm our findings in the future.
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Affiliation(s)
- Xiao-Bin Wang
- Center for Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qi-Jun Wu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Fang-Hua Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shuang Zhang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Han-Yuan Wang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ren-Hao Guo
- Center for Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xu Leng
- Center for Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qiang Du
- Center for Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yu-Hong Zhao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Bo-Chen Pan
- Center for Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
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17
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Carvalho MG, Silva KM, Aristizabal VHV, Ortiz PEO, Paranzini CS, Melchert A, Amaro JL, Souza FF. Effects of Obesity and Diabetes on Sperm Cell Proteomics in Rats. J Proteome Res 2021; 20:2628-2642. [PMID: 33705140 DOI: 10.1021/acs.jproteome.0c01044] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Infertility caused by male factors is potentially associated with metabolic disorders such as obesity and/or diabetes. This experimental study was conducted in a male rodent model to assess the effects of different diseases on semen quality and sperm proteomics. Ten Wistar rats were used for each treatment. Rats were fed commercial food provided controllably to the control group and the diabetic group, and a hypercaloric diet supplemented with 5% sucrose in water was provided ad libitum to the obese group for 38 weeks. Diabetes was induced with 35 mg/kg streptozotocin. After euthanasia, testicles, spermatozoa, fat, and blood (serum) samples were collected. Spermatozoa were evaluated for quality and subjected to proteomics analyses. Histology and cytology of the testis, and serum leptin, adiponectin, interleukin 8 (IL-8), blood glucose, and testosterone levels, were also assessed. Body weight, retroperitoneal and testicular fat, and the Lee index were also measured. Obesity and diabetes were induced. The diabetic group showed noticeable changes in spermatogenesis and sperm quality. The mass spectrometry proteomics data have been deposited in Mendeley Data (doi: 10.17632/rfp7kfjcsd.5). Fifteen proteins varied in abundance between groups, especially proteins related to energy production and structural function of the spermatozoa, suggesting disturbances in energy production with a subsequent alteration in sperm motility in both groups, but with a compensatory response in the obese group.
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Affiliation(s)
- Marcos G Carvalho
- Department of Veterinary Surgery and Animal Reproduction, School of Veterinary Medicine and Animal Science, São Paulo State University "Júlio de Mesquita Filho"-UNESP, Rua Prof. Dr. Walter Maurício Correa, s/n, Rubião Junior, 18681-681 Botucatu, São Paulo, Brazil
| | - Kelry M Silva
- Department of Veterinary Surgery and Animal Reproduction, School of Veterinary Medicine and Animal Science, São Paulo State University "Júlio de Mesquita Filho"-UNESP, Rua Prof. Dr. Walter Maurício Correa, s/n, Rubião Junior, 18681-681 Botucatu, São Paulo, Brazil
| | - Viviana H V Aristizabal
- Department of Veterinary Surgery and Animal Reproduction, School of Veterinary Medicine and Animal Science, São Paulo State University "Júlio de Mesquita Filho"-UNESP, Rua Prof. Dr. Walter Maurício Correa, s/n, Rubião Junior, 18681-681 Botucatu, São Paulo, Brazil
| | - Pablo E O Ortiz
- Department of Veterinary Surgery and Animal Reproduction, School of Veterinary Medicine and Animal Science, São Paulo State University "Júlio de Mesquita Filho"-UNESP, Rua Prof. Dr. Walter Maurício Correa, s/n, Rubião Junior, 18681-681 Botucatu, São Paulo, Brazil
| | - Cristiane S Paranzini
- Department of Veterinary Surgery and Animal Reproduction, School of Veterinary Medicine and Animal Science, São Paulo State University "Júlio de Mesquita Filho"-UNESP, Rua Prof. Dr. Walter Maurício Correa, s/n, Rubião Junior, 18681-681 Botucatu, São Paulo, Brazil.,Envol Biomedical, Immokalee, Florida 34143, United States
| | - Alessandra Melchert
- Department of Veterinary Clinical, School of Veterinary Medicine and Animal Science, São Paulo State University "Júlio de Mesquita Filho"-UNESP, 18618-681 Botucatu, São Paulo, Brazil
| | - João L Amaro
- Department of Surgical Specialties and Anesthesiology, Urology, School of Medicine, São Paulo State University ̈Júlio de Mesquita Filho"-UNESP, 18618-687 Botucatu, São Paulo, Brazil
| | - Fabiana F Souza
- Department of Veterinary Surgery and Animal Reproduction, School of Veterinary Medicine and Animal Science, São Paulo State University "Júlio de Mesquita Filho"-UNESP, Rua Prof. Dr. Walter Maurício Correa, s/n, Rubião Junior, 18681-681 Botucatu, São Paulo, Brazil
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He H, Yu F, Shen W, Chen K, Zhang L, Lou S, Zhang Q, Chen S, Yuan X, Jia X, Zhou Y. The Novel Key Genes of Non-obstructive Azoospermia Affect Spermatogenesis: Transcriptomic Analysis Based on RNA-Seq and scRNA-Seq Data. Front Genet 2021; 12:608629. [PMID: 33732283 PMCID: PMC7959792 DOI: 10.3389/fgene.2021.608629] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 02/08/2021] [Indexed: 12/19/2022] Open
Abstract
Non-obstructive azoospermia (NOA) is one of the most important causes of male infertility. It is mainly characterized by the absence of sperm in semen repeatedly or the number of sperm is small and not fully developed. At present, its pathogenesis remains largely unknown. The goal of this study is to identify hub genes that might affect biomarkers related to spermatogenesis. Using the clinically significant transcriptome and single-cell sequencing data sets on the Gene Expression Omnibus (GEO) database, we identified candidate hub genes related to spermatogenesis. Based on them, we performed Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses, protein-protein interaction (PPI) network analysis, principal component analysis (PCA), cell cluster analysis, and pseudo-chronological analysis. We identified a total of 430 differentially expressed genes, of which three have not been reported related to spermatogenesis (C22orf23, TSACC, and TTC25), and the expression of these three hub genes was different in each type of sperm cells. The results of the pseudo-chronological analysis of the three hub genes indicated that TTC25 was in a low expression state during the whole process of sperm development, while the expression of C22orf23 had two fluctuations in the differentiating spermatogonia and late primary spermatocyte stages, and TSACC showed an upward trend from the spermatogonial stem cell stage to the spermatogenesis stage. Our research found that the three hub genes were different in the trajectory of sperm development, indicating that they might play important roles in different sperm cells. This result is of great significance for revealing the pathogenic mechanism of NOA and further research.
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Affiliation(s)
- Haihong He
- Department of Emergency Laboratory, Clinical Laboratory Medical Center, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Fan Yu
- Department of Emergency Laboratory, Clinical Laboratory Medical Center, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Wang Shen
- Department of Clinical Laboratory, Affiliated Jiangmen TCM Hospital of Ji'nan University, Jiangmen, China
| | - Keyan Chen
- Department of Emergency Laboratory, Clinical Laboratory Medical Center, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Lijun Zhang
- Department of Emergency Laboratory, Clinical Laboratory Medical Center, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Shuang Lou
- Department of Emergency Laboratory, Clinical Laboratory Medical Center, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Qiaomin Zhang
- Department of Emergency Laboratory, Clinical Laboratory Medical Center, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Siping Chen
- Department of Emergency Laboratory, Clinical Laboratory Medical Center, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Xinhua Yuan
- Department of Emergency Laboratory, Clinical Laboratory Medical Center, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Xingwang Jia
- Department of Emergency Laboratory, Clinical Laboratory Medical Center, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Yiwen Zhou
- Department of Emergency Laboratory, Clinical Laboratory Medical Center, Shenzhen Hospital, Southern Medical University, Shenzhen, China
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19
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Transcriptome Analysis of Testis from HFD-Induced Obese Rats ( Rattus norvigicus) Indicated Predisposition for Male Infertility. Int J Mol Sci 2020; 21:ijms21186493. [PMID: 32899471 PMCID: PMC7554891 DOI: 10.3390/ijms21186493] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 08/23/2020] [Accepted: 08/27/2020] [Indexed: 12/13/2022] Open
Abstract
Obesity is a worldwide life-threatening metabolic disorder, associated with various chronic diseases, including male infertility. Obesity was induced by high fat diet (HFD), and testis RNA was used for the transcriptome analysis using RNAseq via Illumina NovaSeq 6000 System and NovaSeq 6000 Kit. Gene expression level was estimated as FPKM (Fragments Per Kilobase of transcript per Million mapped reads). Differential expressed genes (DEGs) were annotated against gene ontology (GO) and KEGG databases. More than 63.66 million reads per sample were performed with 100 bp cutoff and 6 Gb sequencing depth. Results of this study revealed that 267 GO terms (245 biological processes (BP), 14 cellular components (CC), eight molecular functions (MF)), and 89 KEGG pathways were significantly enriched. Moreover, total numbers of 136 genes were differentially expressed (107 upregulated, 29 downregulated) with |FC| ≥ 2 and bh adjusted <0.05. Interesting DEGs were detected, including obesity and lipid metabolism-related genes, immune response-related genes, cytochrome P450 genes, including aromatase were upregulated, whereas genes related to male fertility and fertilization, cell adhesion, and olfactory receptors were downregulated. The combined expression pattern of the DEGs in obese animals indicated an increase in cholesterol metabolism. Furthermore, high aromatase activity enhances the testosterone turnover into estradiol and lowers the testosterone/estradiol (T/E) ratio, which ultimately reduces fertility. In addition, downregulation of cadherens junction components genes leads to the pre-mature release of sperm from Sertoli cells resulting in the reduction of fertility. Moreover, the downregulation of olfactory receptor genes reduces the chemotaxis capacity of sperms in tracking the oocyte for fertilization, which reduces male fertility. Furthermore, various obesity molecular markers were detected in our transcriptome. The results of this study will enhance our understanding of the molecular network of obesity development, development of obesity novel molecular diagnosis markers, molecular bases of obesity-induced infertility, and the development of anti-obesity drugs.
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20
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Wu YQ, Rao M, Hu SF, Ke DD, Zhu CH, Xia W. Effect of transient scrotal hyperthermia on human sperm: an iTRAQ-based proteomic analysis. Reprod Biol Endocrinol 2020; 18:83. [PMID: 32787870 PMCID: PMC7422586 DOI: 10.1186/s12958-020-00640-w] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 07/29/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Through this prospective study, we aimed to explore the change of molecular modification after the transient scrotal hyperthermia on human sperm. METHODS Ten healthy subjects selected with strict screening criteria underwent testicular warming in a 43 °C water bath for 30 min a day for 10 consecutive days. Semen samples were collected 2 weeks before the first heat treatment and 6 weeks after the first heat treatment. Proteins from the samples were labeled with isobaric tags for relative and absolute quantitation and analyzed by two-dimensional liquid chromatography-tandem mass spectrometry. RESULTS In contrast to the control, of the 3446 proteins identified, 61 proteins were deregulated: 28 were up-regulated and 33 were down-regulated. Approximately 95% of the differentially expressed proteins were found to participate in spermatogenesis, fertilization, or other aspects of reproduction. In particular, the expression of sperm motility and energy metabolism-related proteins AKAP4, SPESP1, ODF1, ODF2, GAPDHS, and ACTRT2, validated by western blotting of the proteins obtained from human and mouse samples, tended to be reduced under scrotal hyperthermia. CONCLUSIONS The results indicated that the proteins AKAP4, ODF1, ODF2, GAPDHS, SPESP1, and ACTRT2, play an important role in the heat-induced reversible reduction in sperm concentration and motility and have the potential to be the biomarkers and clinical targets for scrotal heat treatment induced male infertility.
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Affiliation(s)
- Yan-Qing Wu
- Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Meng Rao
- Department of reproduction and genetics, the first affiliated hospital of Kunming medical university, Kunming, People's Republic of China
| | - Shi-Fu Hu
- Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Dan-Dan Ke
- Department of Obstetrics and Gynecological Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Chang-Hong Zhu
- Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
- Reproductive Medicine Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Wei Xia
- Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
- Reproductive Medicine Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
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21
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Liu Y, Fan J, Yan Y, Dang X, Zhao R, Xu Y, Ding Z. JMY expression by Sertoli cells contributes to mediating spermatogenesis in mice. FEBS J 2020; 287:5478-5497. [PMID: 32279424 DOI: 10.1111/febs.15328] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 02/27/2020] [Accepted: 04/06/2020] [Indexed: 12/21/2022]
Abstract
Sertoli cells are crucial for spermatogenesis in the seminiferous epithelium because their actin cytoskeleton supports vesicular transport, cell junction formation, protein anchoring, and spermiation. Here, we show that a junction-mediating and actin-regulatory protein (JMY) affects the blood-tissue barrier (BTB) function through remodeling of the Sertoli cell junctional integrity and it also contributes to controlling endocytic vesicle trafficking. These functions are critical for the maintenance of sperm fertility since loss of Sertoli cell-specific Jmy function induced male subfertility in mice. Specifically, these mice have (a) impaired BTB integrity and spermatid adhesion in the seminiferous tubules; (b) high incidence of sperm structural deformity; and (c) reduced sperm count and poor sperm motility. Moreover, the cytoskeletal integrity was compromised along with endocytic vesicular trafficking. These effects impaired junctional protein recycling and reduced Sertoli cell BTB junctional integrity. In addition, JMY interaction with actin-binding protein candidates α-actinin1 and sorbin and SH3 domain containing protein 2 was related to JMY activity, and in turn, actin cytoskeletal organization. In summary, JMY affects the control of spermatogenesis through the regulation of actin filament organization and endocytic vesicle trafficking in Sertoli cells.
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Affiliation(s)
- Yue Liu
- Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, China
| | - Jiaying Fan
- Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, China.,Center for Experimental Medical Science Education, Shanghai Jiao Tong University School of Medicine, China
| | - Yan Yan
- Department of Clinical Medicine, Shanghai Jiao Tong University School of Medicine, China
| | - Xuening Dang
- Department of Clinical Medicine, Shanghai Jiao Tong University School of Medicine, China
| | - Ran Zhao
- Department of Clinical Medicine, Shanghai Jiao Tong University School of Medicine, China
| | - Yimei Xu
- Department of Clinical Medicine, Shanghai Jiao Tong University School of Medicine, China
| | - Zhide Ding
- Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, China
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22
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Pini T, Parks J, Russ J, Dzieciatkowska M, Hansen KC, Schoolcraft WB, Katz-Jaffe M. Obesity significantly alters the human sperm proteome, with potential implications for fertility. J Assist Reprod Genet 2020; 37:777-787. [PMID: 32026202 PMCID: PMC7183029 DOI: 10.1007/s10815-020-01707-8] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Accepted: 01/30/2020] [Indexed: 11/25/2022] Open
Abstract
PURPOSE In men, obesity may lead to poor semen parameters and reduced fertility. However, the causative links between obesity and male infertility are not totally clear, particularly on a molecular level. As such, we investigated how obesity modifies the human sperm proteome, to elucidate any important implications for fertility. METHODS Sperm protein lysates from 5 men per treatment, classified as a healthy weight (body mass index (BMI) ≤ 25 kg/m2) or obese (BMI ≥ 30 kg/m2), were FASP digested, submitted to liquid chromatography tandem mass spectrometry, and compared by label-free quantification. Findings were confirmed for several proteins by qualitative immunofluorescence and a quantitative protein immunoassay. RESULTS A total of 2034 proteins were confidently identified, with 24 proteins being significantly (p < 0.05) less abundant (fold change < 0.05) in the spermatozoa of obese men and 3 being more abundant (fold change > 1.5) compared with healthy weight controls. Proteins with altered abundance were involved in a variety of biological processes, including oxidative stress (GSS, NDUFS2, JAGN1, USP14, ADH5), inflammation (SUGT1, LTA4H), translation (EIF3F, EIF4A2, CSNK1G1), DNA damage repair (UBEA4), and sperm function (NAPA, RNPEP, BANF2). CONCLUSION These results suggest that oxidative stress and inflammation are closely tied to reproductive dysfunction in obese men. These processes likely impact protein translation and folding during spermatogenesis, leading to poor sperm function and subfertility. The observation of these changes in obese men with no overt andrological diagnosis further suggests that traditional clinical semen assessments fail to detect important biochemical changes in spermatozoa which may compromise fertility.
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Affiliation(s)
- T Pini
- Colorado Center for Reproductive Medicine, Lone Tree, CO, 80124, USA.
| | - J Parks
- Colorado Center for Reproductive Medicine, Lone Tree, CO, 80124, USA
| | - J Russ
- Colorado Center for Reproductive Medicine, Lone Tree, CO, 80124, USA
| | - M Dzieciatkowska
- School of Medicine Biological Mass Spectrometry Facility, University of Colorado, Aurora, CO, 80045, USA
| | - K C Hansen
- School of Medicine Biological Mass Spectrometry Facility, University of Colorado, Aurora, CO, 80045, USA
| | - W B Schoolcraft
- Colorado Center for Reproductive Medicine, Lone Tree, CO, 80124, USA
| | - M Katz-Jaffe
- Colorado Center for Reproductive Medicine, Lone Tree, CO, 80124, USA
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23
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Agarwal A, Panner Selvam MK, Baskaran S. Proteomic Analyses of Human Sperm Cells: Understanding the Role of Proteins and Molecular Pathways Affecting Male Reproductive Health. Int J Mol Sci 2020; 21:ijms21051621. [PMID: 32120839 PMCID: PMC7084638 DOI: 10.3390/ijms21051621] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Revised: 02/22/2020] [Accepted: 02/24/2020] [Indexed: 12/12/2022] Open
Abstract
Human sperm proteomics research has gained increasing attention lately, which provides complete information about the functional state of the spermatozoa. Changes in the sperm proteome are evident in several male infertility associated conditions. Global proteomic tools, such as liquid chromatography tandem mass spectrometry and matrix-assisted laser desorption/ionization time-of-flight, are used to profile the sperm proteins to identify the molecular pathways that are defective in infertile men. This review discusses the use of proteomic techniques to analyze the spermatozoa proteome. It also highlights the general steps involved in global proteomic approaches including bioinformatic analysis of the sperm proteomic data. Also, we have presented the findings of major proteomic studies and possible biomarkers in the diagnosis and therapeutics of male infertility. Extensive research on sperm proteome will help in understanding the role of fertility associated sperm proteins. Validation of the sperm proteins as biomarkers in different male infertility conditions may aid the physician in better clinical management.
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24
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First Insights on the Presence of the Unfolded Protein Response in Human Spermatozoa. Int J Mol Sci 2019; 20:ijms20215518. [PMID: 31694346 PMCID: PMC6861958 DOI: 10.3390/ijms20215518] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Revised: 10/31/2019] [Accepted: 11/04/2019] [Indexed: 01/04/2023] Open
Abstract
The unfolded protein response (UPR) is involved in protein quality control and is activated in response to several stressors. Although in testis the UPR mechanisms are well described, their presence in spermatozoa is contentious. We aimed to investigate the presence of UPR-related proteins in human sperm and the impact of oxidative stress induction in UPR activation. To identify UPR-related proteins in human sperm, a bioinformatic approach was adopted. To explore the activation of UPR, sperm were exposed to hydrogen peroxide (H2O2) and motility, vitality, and the levels of UPR-related proteins were assessed. We identified 97 UPR-related proteins in human sperm and showed, for the first time, the presence of HSF1, GADD34, and phosphorylated eIF2α. Additionally, the exposure of human sperm to H2O2 resulted in a significant decrease in sperm viability and motility and an increase in the levels of HSF1, HSP90, HSP60, HSP27, and eIF2α; all proteins involved in sensing and response to unfolded proteins. This study gave us a first insight into the presence of UPR mechanisms in the male gamete. However, the belief that sperm are devoid of transcription and translation highlight the need to clarify if these pathways are activated in sperm in the same way as in somatic cells.
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25
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Liu Y, Wang JX, Nie ZY, Wen Y, Jia XJ, Zhang LN, Duan HJ, Shi YH. Upregulation of ERp57 promotes clear cell renal cell carcinoma progression by initiating a STAT3/ILF3 feedback loop. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2019; 38:439. [PMID: 31747963 PMCID: PMC6864981 DOI: 10.1186/s13046-019-1453-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Accepted: 10/16/2019] [Indexed: 01/09/2023]
Abstract
Background ERp57 dysfunction has been shown to contribute to tumorigenesis in multiple malignances. However, the role of ERp57 in clear cell renal carcinoma (ccRCC) remains unclear. Methods Cell proliferation ability was measured by MTT and colony forming assays. Western blotting and quantitative real-time PCR (qRT-PCR) were performed to measure protein and mRNA expression. Co-immunoprecipitation (CoIP) and proximity ligation assay (PLA) were performed to detect protein-protein interaction. Chromatin immunoprecipitation (ChIP), ribonucleoprotein immunoprecipitation (RIP), and oligo pull-down were used to confirm DNA–protein and RNA–protein interactions. Promoter luciferase analysis was used to detect transcription factor activity. Results Here we found ERp57 was overexpressed in ccRCC tissues, and the higher levels of ERp57 were correlated with poor survival in patients with ccRCC. In vivo and in vitro experiments showed that ccRCC cell proliferation was enhanced by ERp57 overexpression and inhibited by ERp57 deletion. Importantly, we found ERp57 positively regulated ILF3 expression in ccRCC cells. Mechanically, ERp57 was shown to bind to STAT3 protein and enhance the STAT3-mediated transcriptional activity of ILF3. Furthermore, ILF3 levels were increased in ccRCC tissues and associated with poor prognosis. Interestingly, we revealed that ILF3 could bind to ERp57 and positively regulate its expression by enhancing its mRNA stability. Furthermore, ccRCC cell proliferation was moderated via the ERp57/STAT3/ILF3 feedback loop. Conclusions In summary, our results indicate that the ERp57/STAT3/ILF3 feedback loop plays a key role in the oncogenesis of ccRCC and provides a potential therapeutic target for ccRCC treatment.
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Affiliation(s)
- Yan Liu
- Department of Pathology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.,Department of Anesthesiology, The 4th Hospital of Hebei Medical University, 169 Tianshan Street , 050000, Shijiazhuang, People's Republic of China
| | - Jian-Xing Wang
- Department of Pathology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.,Department of Otolaryngology, The Second Hospital of Hebei Medical University, 215 Heping West Road Shijiazhuang, 050000, Shijiazhuang, People's Republic of China
| | - Zi-Yuan Nie
- Department of Hematology, The Second Hospital of Hebei Medical University, 215 Heping West Road Shijiazhuang, 050000, Shijiazhuang, People's Republic of China
| | - Yue Wen
- Department of Pathology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China
| | - Xin-Ju Jia
- Department of Endocrinology, The First Hospital of Hebei Medical University, 89 Donggang Road Shijiazhuang, 050000, Shijiazhuang, People's Republic of China
| | - Li-Na Zhang
- Department of Pathology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China
| | - Hui-Jun Duan
- Department of Pathology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
| | - Yong-Hong Shi
- Department of Pathology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
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Peng Y, Zhao W, Qu F, Jing J, Hu Y, Liu Y, Ding Z. Proteomic alterations underlie an association with teratozoospermia in obese mice sperm. Reprod Biol Endocrinol 2019; 17:82. [PMID: 31651332 PMCID: PMC6813985 DOI: 10.1186/s12958-019-0530-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Accepted: 10/02/2019] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Obesity is a worldwide crisis impairing human health. In this condition, declines in sperm quality stem from reductions in sperm concentration, motility and increase in sperm deformity. The mechanism underlying these alterations remains largely unknown. This study, determined if obesity-associated proteomic expression patterns in mice sperm parallel those in spermatozoa obtained from obese humans. METHODS An obese mouse model was established via feeding a high-fat diet (HFD). Histological analysis identified testicular morphology and a computer assisted semen analyzer (CASA) evaluated sperm parameters. Proteome analysis was performed using a label-free quantitative LC-MS/MS system. Western blot, immunohistochemical and immunofluorescent analyses characterized protein expression levels and localization in testis, sperm and clinical samples. RESULTS Bodyweight gains on the HFD induced hepatic steatosis. Declines in sperm motility accompanied sperm deformity development. Differential proteomic analysis identified reduced cytoskeletal proteins, centrosome and spindle pole associated protein 1 (CSPP1) and Centrin 1 (CETN1), in sperm from obese mice. In normal weight mice, both CSPP1 and CETN1 were localized in the spermatocytes and spermatids. Their expression was appreciable in the post-acrosomal region parallel to the microtubule tracks of the manchette structure in spermatids, which affects spermatid head shaping and morphological maintenance. Moreover, CSPP1 was localized in the head-tail coupling apparatus of the mature sperm, while CETN1 expression was delimited to the post-acrosomal region within the sperm head. Importantly, sperm CSPP1 and CETN1 abundance in both the overweight and obese males decreased in comparison with that in normal weight men. CONCLUSION These findings show that regionally distinct expression and localization of CETN1 and CSPP1 is strongly related to spermiogenesis and sperm morphology maintaining. Obesity is associated with declines in the CETN1 and CSPP1 abundance and compromise of both sperm morphology in mice and relevant clinical samples. This parallelism between altered protein expression in mice and humans suggests that these effects may contribute to poor sperm quality including increased deformity.
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Affiliation(s)
- Yuanhong Peng
- Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Wenzhen Zhao
- Department of Histology and Embryology, School of Basic Medical Science, Dali University, Dali, 671000, Yunnan, China
- Institute of Reproductive Medicine, Dali University, Dali, 671000, Yunnan, China
| | - Fei Qu
- Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Jia Jing
- Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Yanqin Hu
- Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Yue Liu
- Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
| | - Zhide Ding
- Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
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27
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How much does obesity affect the male reproductive function? INTERNATIONAL JOURNAL OF OBESITY SUPPLEMENTS 2019; 9:50-64. [PMID: 31391924 DOI: 10.1038/s41367-019-0008-2] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Obesity is considered a worldwide epidemic disease. Many pathological conditions have been associated to obesity but the evidence relating to impaired fertility in males with obesity are contrasting. The aim of this review was to evaluate the interplay between obesity and male fertility, analyzing evidence from in vitro and in vivo studies to clinical trials. Obesity seems to be responsible of secondary hypogonadism. Here, we propose a new classification including central, peripheral and testicular factors that may affect the hypothalamic-pituitary-gonadal axis. Moreover, some studies demonstrated a direct action of obesity on sperm count and sperm characteristics, mediated by impaired Sertoli cells function, increased scrotal temperature, oxidative stress and accumulation of toxic substances and liposoluble endocrine disruptors in fat tissue. Recent studies have explored obesity-related epigenetic effects in sperm cells which may cause diseases in offspring. Moreover, not only in females but also males, obesity has been linked to reduced outcomes of in vitro fertilization, with a reduction of pregnancy rate and an increase of pregnancy loss. Finally, we reviewed the effects of weight modifications through diet or bariatric surgery on obesity-related reproductive dysfunction. In this regard, several studies have demonstrated that weight loss has been associated with a restoration of gonadal hormones levels.
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28
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Protein profile of Dabry's sturgeon (Acipenser dabryanus) spermatozoa and relationship to sperm quality. Anim Reprod Sci 2018; 201:1-11. [PMID: 30587384 DOI: 10.1016/j.anireprosci.2018.12.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Revised: 10/25/2018] [Accepted: 12/05/2018] [Indexed: 11/23/2022]
Abstract
Knowledge of conditions affecting sperm quality is essential for efficient culture of fish for commercial purposes and conservation of species. Two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry were used to characterize the proteomic profile of Acipenser dabryanus spermatozoa relative to motility and fertilization capacity. There were differential amounts of protein in 313 spots in spermatozoa of males classified to have relatively greater or lesser spermatozoa quality. The functions of 43 of 50 selected proteins were identified. The proteins in 14 spots were involved in metabolism, and of these, proteins in 11 spots were highly abundant in spermatozoa of males categorized to have spermatozoa of greater quality, including pyruvate kinase, enolase B, phosphoglycerate kinase, lactate dehydrogenase, cytosolic malate dehydrogenase, brain creatine kinase b, Ckmb protein, and nucleoside diphosphate kinase. The proteins involved in mechanics of flagellum movement were identified, including the dynein intermediate chain, radial spoke head 1 homolog; ropporin-1-like, Bardet-Biedl syndrome 5, ADP-ribosylation factor-like protein 3, tektin-4, gamma-actin, and tubulin cytoskeleton proteins to be differentially abundant in spermatozoa that were classified relatively greater or lesser quality. Heat shock proteins, copper/zinc superoxide dismutase and peroxiredoxins, which are involved in stress response were of differential abundance in spermatozoa from males with spermatozoa in the two different classification groups. Proteins were also detected that are involved in protein folding and binding, or hydrolase activity. The results are valuable for the prediction of sperm quality and for reproduction management in A. dabryanus and other threatened species.
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Masood A, Benabdelkamel H, Alfadda AA. Obesity Proteomics: An Update on the Strategies and Tools Employed in the Study of Human Obesity. High Throughput 2018; 7:ht7030027. [PMID: 30213114 PMCID: PMC6164994 DOI: 10.3390/ht7030027] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 08/30/2018] [Accepted: 09/10/2018] [Indexed: 02/07/2023] Open
Abstract
Proteomics has become one of the most important disciplines for characterizing cellular protein composition, building functional linkages between protein molecules, and providing insight into the mechanisms of biological processes in a high-throughput manner. Mass spectrometry-based proteomic advances have made it possible to study human diseases, including obesity, through the identification and biochemical characterization of alterations in proteins that are associated with it and its comorbidities. A sizeable number of proteomic studies have used the combination of large-scale separation techniques, such as high-resolution two-dimensional gel electrophoresis or liquid chromatography in combination with mass spectrometry, for high-throughput protein identification. These studies have applied proteomics to comprehensive biochemical profiling and comparison studies while using different tissues and biological fluids from patients to demonstrate the physiological or pathological adaptations within their proteomes. Further investigations into these proteome-wide alterations will enable us to not only understand the disease pathophysiology, but also to determine signature proteins that can serve as biomarkers for obesity and related diseases. This review examines the different proteomic techniques used to study human obesity and discusses its successful applications along with its technical limitations.
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Affiliation(s)
- Afshan Masood
- Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia.
| | - Hicham Benabdelkamel
- Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia.
| | - Assim A Alfadda
- Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia.
- Department of Medicine, College of Medicine, King Saud University, P.O. Box 2925 (38), Riyadh 11461, Saudi Arabia.
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Castillo J, Jodar M, Oliva R. The contribution of human sperm proteins to the development and epigenome of the preimplantation embryo. Hum Reprod Update 2018; 24:535-555. [DOI: 10.1093/humupd/dmy017] [Citation(s) in RCA: 83] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Accepted: 04/25/2018] [Indexed: 02/07/2023] Open
Affiliation(s)
- Judit Castillo
- Molecular Biology of Reproduction and Development Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Fundació Clínic per a la Recerca Biomèdica, Faculty of Medicine, University of Barcelona, Casanova, Barcelona, Spain
| | - Meritxell Jodar
- Molecular Biology of Reproduction and Development Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Fundació Clínic per a la Recerca Biomèdica, Faculty of Medicine, University of Barcelona, Casanova, Barcelona, Spain
| | - Rafael Oliva
- Molecular Biology of Reproduction and Development Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Fundació Clínic per a la Recerca Biomèdica, Faculty of Medicine, University of Barcelona, Casanova, Barcelona, Spain
- Biochemistry and Molecular Genetics Service, Hospital Clínic, Villarroel, Barcelona, Spain
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Xu Y, Fan Y, Fan W, Jing J, Xue K, Zhang X, Ye B, Ji Y, Liu Y, Ding Z. RNASET2 impairs the sperm motility via PKA/PI3K/calcium signal pathways. Reproduction 2018; 155:383-392. [DOI: 10.1530/rep-17-0746] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 02/13/2018] [Indexed: 12/30/2022]
Abstract
Asthenozoospermia is one of the leading causes of male infertility owing to a decline in sperm motility. Herein, we determined if there is a correlation between RNASET2 content on human spermatozoa and sperm motility in 205 semen samples from both asthenozoospermia patients and normozoospermia individuals. RNASET2 content was higher in sperm from asthenozoospermia patients than in normozoospermia individuals. On the other hand, its content was inversely correlated with sperm motility as well as progressive motility. Moreover, the inhibitory effect of RNASET2 on sperm motility was induced by incubating normozoospermic sperm with RNase T2 protein. Such treatment caused significant declines in intracellular spermatozoa PKA activity, PI3K activity and calcium level, which resulted in severely impaired sperm motility, and the sperm motility was largely rescued by cAMP supplementation. Finally, protein immunoprecipitation and mass spectrometry identified proteins whose interactions with RNASET2 were associated with declines in human spermatozoa motility. AKAP4, a protein regulating PKA activity, coimmunoprecipated with RNASET2 and they colocalized with one another in the sperm tail, which might contribute to reduced sperm motility. Thus, RNASET2 may be a novel biomarker of asthenozoospermia. Increases in RNASET2 can interact with AKAP4 in human sperm tail and subsequently reduce sperm motility by suppressing PKA/PI3K/calcium signaling pathways.
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Intasqui P, Agarwal A, Sharma R, Samanta L, Bertolla RP. Towards the identification of reliable sperm biomarkers for male infertility: A sperm proteomic approach. Andrologia 2017; 50. [DOI: 10.1111/and.12919] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/01/2017] [Indexed: 01/20/2023] Open
Affiliation(s)
- P. Intasqui
- American Center for Reproductive Medicine; Cleveland Clinic; Cleveland OH USA
- Department of Surgery; Division of Urology; Human Reproduction Section; Sao Paulo Federal University - Sao Paulo Hospital; Sao Paulo Brazil
| | - A. Agarwal
- American Center for Reproductive Medicine; Cleveland Clinic; Cleveland OH USA
| | - R. Sharma
- American Center for Reproductive Medicine; Cleveland Clinic; Cleveland OH USA
| | - L. Samanta
- Department of Zoology; Ravenshaw University; Cuttack India
| | - R. P. Bertolla
- Department of Surgery; Division of Urology; Human Reproduction Section; Sao Paulo Federal University - Sao Paulo Hospital; Sao Paulo Brazil
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Liu Y, Ding Z. Obesity, a serious etiologic factor for male subfertility in modern society. Reproduction 2017; 154:R123-R131. [DOI: 10.1530/rep-17-0161] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Revised: 07/02/2017] [Accepted: 07/26/2017] [Indexed: 12/14/2022]
Abstract
Obesity, defined as excessive accumulation of fat in adipose tissue, is a metabolic disorder resulting from behavioral, environmental and heritable causes. Obesity increases the risks of hypertension, diabetes, cardiovascular disease, sleep apnea, respiratory problems, osteoarthritis and cancer. Meanwhile, the negative impact of obesity on male reproduction is gradually recognized. According to the clinical investigations and animal experiments, obesity is correlated with reductions in sperm concentration and motility, increase in sperm DNA damage and changes in reproductive hormones. Several mechanisms can elucidate the effects of obesity on sperm functions and male subfertility, i.e., the excessive conversion of androgens into estrogens in redundant adipose tissue causes sexual hormone imbalance, subsequently resulting in hypogonadism. Secondly, adipokines produced by adipose tissue induce severe inflammation and oxidative stress in male reproductive tract, directly impairing testicular and epididymal tissues. Moreover, increased scrotal adiposity leads to increase gonadal heat, continuously hurting spermatogenesis. Therefore, obesity alters the systematic and regional environment crucial for spermatogenesis in testis and sperm maturation in epididymis, and finally results in poor sperm quality including decreased sperm motility, abnormal sperm morphology and acrosome reaction, changed membrane lipids and increased DNA damage. Furthermore, recent studies indicate that epigenetic changes may be a consequence of increased adiposity. A major effort to identify epigenetic determinants of obesity revealed that sperm DNA methylation and non-coding RNA modification are associated with BMI changes and proposed to inherit metabolic comorbidities across generations. This review will explain how obesity-related changes in males to influence sperm function and male fertility as well.
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Ortega-Ferrusola C, Gil MC, Rodríguez-Martínez H, Anel L, Peña FJ, Martín-Muñoz P. Flow cytometry in Spermatology: A bright future ahead. Reprod Domest Anim 2017; 52:921-931. [DOI: 10.1111/rda.13043] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2017] [Accepted: 06/26/2017] [Indexed: 12/31/2022]
Affiliation(s)
- C Ortega-Ferrusola
- Reproduction and Obstetrics Department of Animal Medicine and Surgery; University of León; León Spain
| | - MC Gil
- Laboratory of Equine Reproduction and Equine Spermatology; Veterinary Teaching Hospital; University of Extremadura; Cáceres Spain
| | - H Rodríguez-Martínez
- Department of Clinical and Experimental Medicine; Faculty of Health Sciences Linköping University; Linköping Sweden
| | - L Anel
- Reproduction and Obstetrics Department of Animal Medicine and Surgery; University of León; León Spain
| | - FJ Peña
- Laboratory of Equine Reproduction and Equine Spermatology; Veterinary Teaching Hospital; University of Extremadura; Cáceres Spain
| | - P Martín-Muñoz
- Laboratory of Equine Reproduction and Equine Spermatology; Veterinary Teaching Hospital; University of Extremadura; Cáceres Spain
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Abstract
The protein disulfide isomerase (PDI) gene family is a protein family classically characterized by endoplasmic reticulum (ER) localization and isomerase and redox activity. ERp57, a prominent multifunctional member of the PDI family, is detected at various levels in multiple cellular localizations outside of the ER. ERp57 has been functionally linked to a host of physiological processes and numerous studies have demonstrated altered expression and aberrant functionality of ERp57 in association with diverse pathological states. Here, we summarize available knowledge of ERp57's functions in subcellular compartments and the roles of dysregulated ERp57 in various diseases toward an emphasis on the potential utility of therapeutic development of ERp57.
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Affiliation(s)
- Aubryanna Hettinghouse
- Department of Orthopaedic Surgery, New York University Medical Center, New York, NY 10003, USA
| | - Ronghan Liu
- Department of Orthopaedic Surgery, New York University Medical Center, New York, NY 10003, USA
| | - Chuan-Ju Liu
- Department of Orthopaedic Surgery, New York University Medical Center, New York, NY 10003, USA; Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
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Schorr-Lenz AM, Alves J, Henckes NAC, Seibel PM, Benham AM, Bustamante-Filho IC. GnRH immunization alters the expression and distribution of protein disulfide isomerases in the epididymis. Andrology 2016; 4:957-63. [DOI: 10.1111/andr.12205] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Revised: 03/18/2016] [Accepted: 04/02/2016] [Indexed: 01/03/2023]
Affiliation(s)
- A. M. Schorr-Lenz
- Centro de Ciências Biológicas e da Saúde; Univates; Lajeado RS Brazil
| | - J. Alves
- Centro de Ciências Biológicas e da Saúde; Univates; Lajeado RS Brazil
| | - N. A. C. Henckes
- Centro de Ciências Biológicas e da Saúde; Univates; Lajeado RS Brazil
| | - P. M. Seibel
- Centro de Ciências Biológicas e da Saúde; Univates; Lajeado RS Brazil
| | - A. M. Benham
- School of Biological and Biomedical Sciences; Durham University; Durham UK
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Rajpert-De Meyts E, Carrell DT. Andrology Award 2015. Andrology 2016; 4:361-2. [PMID: 27147396 DOI: 10.1111/andr.12207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- E Rajpert-De Meyts
- Department of Growth and Reproduction, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark
| | - D T Carrell
- Departments of Surgery (Urology), Obstetrics and Gynecology, and Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA
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Marchiani S, Tamburrino L, Muratori M, Baldi E. New insights in sperm biology: How benchside results in the search for molecular markers may help understand male infertility. World J Transl Med 2016; 5:26-36. [DOI: 10.5528/wjtm.v5.i1.26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Revised: 01/22/2016] [Accepted: 02/17/2016] [Indexed: 02/06/2023] Open
Abstract
The male factor is responsible for about 40% of couple infertility cases and such percentage is expected to increase in the future because of several likely factors including the presence of endocrine disruptors in the environment, changes in lifestyle habits and advanced couple aging. How such factors affect male fertility status, however, should be clarified. Most studies on male fertility status have focused on parameters analyzed using a spermiogram test, the primary diagnostic tool in the routine assessment of male infertility, which is, however, poorly predictive of both natural and medically assisted conception. For these reasons it is mandatory for the scientific community to identify new molecular markers to incorporate into the existing diagnostic tests of male fertility. Ideally, such markers would be detected in mature spermatozoa to avoid invasive procedures for the patient. This review summarizes the recent advancements in benchside approaches that appear most promising for the development of new diagnostic sperm fertility tests, or identification of therapeutic targets, and, illustrates their advantages and limits.
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McPherson NO, Bell VG, Zander-Fox DL, Fullston T, Wu LL, Robker RL, Lane M. When two obese parents are worse than one! Impacts on embryo and fetal development. Am J Physiol Endocrinol Metab 2015. [PMID: 26199280 DOI: 10.1152/ajpendo.00230.2015] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The prevalence of overweight and obesity in reproductive-age adults is increasing worldwide. While the effects of either paternal or maternal obesity on gamete health and subsequent fertility and pregnancy have been reported independently, the combination of having both parents overweight/obese on fecundity and offspring health has received minimal attention. Using a 2 × 2 study design in rodents we established the relative contributions of paternal and maternal obesity on fetal and embryo development and whether combined paternal and maternal obesity had an additive effect. Here, we show that parental obesity reduces fetal and placental weights without altering pregnancy establishment and is not dependent on an in utero exposure to a high-fat diet. Interestingly combined parental obesity seemed to accumulate both the negative influences of paternal and maternal obesity had alone on embryo and fetal health rather than an amplification, manifested as reduced embryo developmental competency, reduced blastocyst cell numbers, impaired mitochondrial function, and alterations to active and repressive embryonic chromatin marks, resulting in aberrant placental gene expression and reduced fetal liver mtDNA copy numbers. Further understanding both the maternal cytoplasmic and paternal genetic interactions during this early developmental time frame will be vital for understanding how developmental programming is regulated and for the proposition of interventions to mitigate their effects.
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Affiliation(s)
- N O McPherson
- School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, South Australia, Australia; Freemasons Centre for Men's Health, University of Adelaide, South Australia, Australia; Repromed, Dulwich, South Australia, Australia; and
| | - V G Bell
- School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, South Australia, Australia; Freemasons Centre for Men's Health, University of Adelaide, South Australia, Australia; Repromed, Dulwich, South Australia, Australia; and
| | - D L Zander-Fox
- School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, South Australia, Australia; Repromed, Dulwich, South Australia, Australia; and
| | - T Fullston
- School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, South Australia, Australia
| | - L L Wu
- School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, South Australia, Australia
| | - R L Robker
- School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, South Australia, Australia
| | - M Lane
- School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, South Australia, Australia; Monash In Vitro Fertilisation Group, Richmond, Australia
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