Proteomic profile of seminal plasma in adolescents and adults with treated and untreated varicocele

Varicocele, the most important treatable cause of male infertility, is present in 15% of adult males, 35% of men with primary infertility, and 80% of men with secondary infertility. On the other hand, 80% of these men will not present infertility. Therefore, there is a need to differentiate a varicocele that is exerting a deleterious effect that is treatable from a "silent" varicocele. Despite the growing evidence of the cellular effects of varicocele, its underlying molecular mechanisms are still eluding. Proteomics has become a promising area to determine the reproductive biology of semen as well as to improve diagnosis of male infertility. This review aims to discuss the state-of-art in seminal plasma proteomics in patients with varicocele to discuss the challenges in undertaking these studies, as well as the future outlook derived from the growing body of evidence on the seminal proteome.Sao Paulo Research Foundation (FAPESP)National Council for Scientific and Technological Development (CNPq)Univ Fed Sao Paulo, Div Urol, Human Reprod Sect, Dept Surg, R Embau 231, BR-04039060 Sao Paulo, BrazilSao Paulo Hosp, Sao Paulo, BrazilUniv Fed Sao Paulo, Div Urol, Human Reprod Sect, Dept Surg, R Embau 231, BR-04039060 Sao Paulo, BrazilSao Paulo Hosp, Sao Paulo, BrazilFAPESP: 2012/15039-7FAPESP: 2014/11493-0FAPESP: 2014/17185-6CNPq: 306616/2013-0Web of Scienc

Oxidative and functional status of bovine semen cryopreserved in different seasons

In general, Taurus bulls under tropical conditions demonstrate reduced fertility due to heat and oxidative stress on testicular tissue. This high incidence of sperm damage is generally enhanced by the large amount of polyunsaturated fatty acids (PUFA) naturally present in bull sperm. Despite PUFA increase cellular sensitivity to lipid peroxidation, they are essential for membrane fluidity and also promote high cellular protection during cryopreservation process. Some reports related that animals and plants provided from cold weather present higher cellular concentration of PUFA, so the present study aims to compare the effect of the season on sperm quality of Taurus and Zebu bulls. Cryoprotected semen samples of 10 Nelore (Bos taurus indicus) and 10 Simmental (Bos taurus taurus) bulls were analyzed during winter and summer seasons. After freezing-thawing process, semen samples were submitted to sperm motility and vigor analysis, to tests of plasma membrane integrity (MPI–Eosin/Nigrosin), acrosomal integrity (MAI-POPE), DNA fragmentation degree (DNAf-Comet Assay) and high mitochondrial activity (ACM-DAB). Moreover, frozen-thawed semen samples were induced to lipid peroxidation for measurement of thiobarbituric acid reactive substances (TBARS) and malondialdehyde (MDA) concentration. Higher post-thawing sperm motility (26.50% winter; 13.30% summer) and ACM (22.34% winter; 13.30% summer) were observed during the winter in Nelore group. In Simmental group, no differences were observed for the studied variables. It was concluded that, despite the heat stress, no seasonal effect on sperm quality was observed in Taurus cattle, which may be related to higher concentration of PUFA in seminal composition.Bovinos taurinos, em clima tropical, mostram menores índices de fertilidade devido ao estresse térmico e oxidativo testicular. Essa alta incidência de alterações espermáticas é potencializada pela grande quantidade de ácidos graxos poli-insaturados (PUFA) presentes nos espermatozoides taurinos. Embora os PUFA aumentem a sensibilidade celular à peroxidação lipídica, são essenciais para a maleabilidade de membrana e promovem maior proteção celular durante a criopreservação. Devido aos relatos de que animais e vegetais de clima frio possuem maior concentração de PUFA nas células, o presente estudo teve como objetivo comparar o efeito da estação do ano sobre a qualidade espermática de taurinos e zebuínos. Foram avaliadas amostras criopreservadas de 10 touros da raça Nelore (Bos taurus indicus) e 10 da raça Simental (Bos taurus taurus), coletadas durante inverno e verão. Após a descongelação, foram realizados testes espermáticos de motilidade e vigor, testes de integridade de membrana plasmática (MPI–Eosina/Nigrosina), integridade acrossomal (MAI-POPE), grau de fragmentação de DNA (DNAf-Ensaio Cometa) e atividade citoquímica mitocondrial (ACM-DAB). Adicionalmente, avaliou-se a suscetibilidade das células espermáticas à peroxidação lipídica induzida, pela mensuração das substâncias reativas ao ácido tiobarbitúrico (TBARS) e malondialdeído (MDA). No grupo Nelore, foi observada maior motilidade espermática pós-descongelação (26,50% inverno; 13,30% verão) e maior ACM (22,34% inverno; 13,30% verão) durante o inverno. No grupo Simental, não houve diferença de época do ano nas variáveis. Concluiu-se que, apesar de sofrerem maior estresse térmico, nos animais taurinos não foi observado efeito da estação do ano sobre a qualidade espermática, o que pode estar relacionado a uma maior concentração de PUFA em sua composição seminal

Protocol for developing a core outcome set for male infertility research:an international consensus development study

Abstract STUDY QUESTION We aim to develop, disseminate and implement a minimum data set, known as a core outcome set, for future male infertility research. WHAT IS KNOWN ALREADY Research into male infertility can be challenging to design, conduct and report. Evidence from randomized trials can be difficult to interpret and of limited ability to inform clinical practice for numerous reasons. These may include complex issues, such as variation in outcome measures and outcome reporting bias, as well as failure to consider the perspectives of men and their partners with lived experience of fertility problems. Previously, the Core Outcome Measure for Infertility Trials (COMMIT) initiative, an international consortium of researchers, healthcare professionals and people with fertility problems, has developed a core outcome set for general infertility research. Now, a bespoke core outcome set for male infertility is required to address the unique challenges pertinent to male infertility research. STUDY DESIGN, SIZE, DURATION Stakeholders, including healthcare professionals, allied healthcare professionals, scientists, researchers and people with fertility problems, will be invited to participate. Formal consensus science methods will be used, including the modified Delphi method, modified Nominal Group Technique and the National Institutes of Health’s consensus development conference. PARTICIPANTS/MATERIALS, SETTING, METHODS An international steering group, including the relevant stakeholders outlined above, has been established to guide the development of this core outcome set. Possible core outcomes will be identified by undertaking a systematic review of randomized controlled trials evaluating potential treatments for male factor infertility. These outcomes will be entered into a modified Delphi method. Repeated reflection and re-scoring should promote convergence towards consensus outcomes, which will be prioritized during a consensus development meeting to identify a final core outcome set. We will establish standardized definitions and recommend high-quality measurement instruments for individual core outcomes. STUDY FUNDING/COMPETING INTEREST(S) This work has been supported by the Urology Foundation small project award, 2021. C.L.R.B. is the recipient of a BMGF grant and received consultancy fees from Exscentia and Exceed sperm testing, paid to the University of Dundee and speaking fees or honoraria paid personally by Ferring, Copper Surgical and RBMO. S.B. received royalties from Cambridge University Press, Speaker honoraria for Obstetrical and Gynaecological Society of Singapore, Merk SMART Masterclass and Merk FERRING Forum, paid to the University of Aberdeen. Payment for leadership roles within NHS Grampian, previously paid to self, now paid to University of Aberdeen. An Honorarium is received as Editor in Chief of Human Reproduction Open. M.L.E. is an advisor to the companies Hannah and Ro. B.W.M. received an investigator grant from the NHMRC, No: GNT1176437 is a paid consultant for ObsEva and has received research funding from Ferring and Merck. R.R.H. received royalties from Elsevier for a book, consultancy fees from Glyciome, and presentation fees from GryNumber Health and Aytu Bioscience. Aytu Bioscience also funded MiOXYS systems and sensors. Attendance at Fertility 2020 and Roadshow South Africa by Ralf Henkel was funded by LogixX Pharma Ltd. R.R.H. is also Editor in Chief of Andrologia and has been an employee of LogixX Pharma Ltd. since 2020. M.S.K. is an associate editor with Human Reproduction Open. K.Mc.E. received an honoraria for lectures from Bayer and Pharmasure in 2019 and payment for an ESHRE grant review in 2019. His attendance at ESHRE 2019 and AUA 2019 was sponsored by Pharmasure and Bayer, respectively. The remaining authors declare no competing interests. TRIAL REGISTRATION NUMBER Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586. TRIAL REGISTRATION DATE N/A. DATE OF FIRST PATIENT’S ENROLMENT N/A

Sperm proteomics: potential impact on male infertility treatment

Spermatozoa are unique cells that have highly compact DNA, motility (and hypermotility) patterns, a specific morphology, localized mitochondria and an apical acrosome. They are the end product of a dynamic process termed spermatogenesis. Sperm are therefore produced with specific proteins in order to effect different traits, such as the presence of cysteine-rich protamines in DNA, which effectively compacts DNA. Moreover, specific proteins are transferred during epididymal maturation and after ejaculation in order to render sperm capable of undergoing post-ejaculatory alterations, generally termed capacitation, which confers capacity to fertilize a mature oocyte. In addition, sperm exhibit several post-translational modifications, which are fundamental to their function, such as SUMOylation and ubiquitination. Discussed in this review is the current knowledge of the sperm proteome in terms of its composition and the function that these proteins determine, as well as their post-translational modifications and how these alter sperm functional integrity. Studies are emphasized that focus on shotgun proteomics - untargeted determination of the protein constituent of a cell in a given biological condition - and technologies currently applied toward that end are reviewed.American Center for Reproductive Medicine, Cleveland ClinicCleveland Clin, Amer Ctr Reprod Med, Dept Urol, Cleveland, OH 44106 USAUniv Fed Sao Paulo, Dept Surg, Div Urol, Human Reprod Sect, Sao Paulo, BrazilRavenshaw Univ, Dept Zool, Sch Life Sci, Cuttack, Orissa, IndiaUniv Fed Sao Paulo, Dept Surg, Div Urol, Human Reprod Sect, Sao Paulo, BrazilWeb of Scienc

Understanding the seminal plasma proteome and its role in male fertility

Résumé Le plasma séminal est un liquide complexe comprenant les sécrétions des vésicules séminales, de la prostate, des glandes bulbo-urétrales, et des sécrétions provenant de la lumière des tubes séminifères/épididymes/canaux déférents. Bien qu’il a été établi que le plasma séminal n’est pas seulement un milieu servant à transporter, protéger et nourrir les spermatozoïdes après l’éjaculation et jusqu’à la fécondation, mais qu’il constitue aussi un modulateur fonctionnel des fonctions spermatiques, il demeure nécessaire de caractiser de manière appropriée la constitution moléculaire du plasma séminal des hommes féconds, et de comprendre comment celle-ci est altérée dans les différentes causes d’infertilité masculine. Le principal objectif de cet article est de passer en revue les études du protéome du plasma séminal, en allant de celles ayant caractérisé une carte protéomique du plasma séminal fertile aux études ayant comparé le plasma séminal d’hommes féconds et inféconds et à celles ayant comparé le plasma séminal d’hommes féconds ou normozoospermiques à celui d’hommes présentant diverses causes d’infertilité. Pour finir, la présente revue est centrée sur l’association entre d’une part la qualité fonctionnelle du sperme et des spermatozoïdes et d’autre part le protéome du plasma séminal dans le but de démontrer les mécanismes cellulaires et moléculaires de l’infertilité masculine. En raison de la nature non ciblée de la majorité des études présentées dans cette revue, et de la grande diversité des techniques utilisées pour étudier la composition protéomique du plasma séminal, de nombreuses protéines différentiellement exprimées ont été observées. Cependant, d’une façon globale, il semblerait qu’il y ait un protéome séminal associé à la fertilité masculine et que des situations biologiques ou des phénotypes cellulaires particuliers l’éloignerait de son point d’équilibre vers des états associés à une production énergétique altérée. De plus, il semblerait exister une composante inflammatoire du plasma séminal chez les hommes infertiles. En conclusion, il existe de nombreuses études centrées sur la composition protéomique du plasma séminal humain; de futures études de confirmation seront utiles à la compréhension des voies spécifiques de l’infertilité dans ses différentes conditions biologiques