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The Molecular Life of Sperm: New Horizons in Male Infertility
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The Molecular Life of Sperm: New Horizons in Male Infertility

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 December 2025 | Viewed by 414

Special Issue Editors

Dr. Mónica Vazquez-Levin

E-Mail Website
Guest Editor
Instituto de Biología y Medicina Experimental (IBYME, CONICET-FIBYME), Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina (CONICET), Buenos Aires 2490, Argentina
Interests: Sperm Biology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Robert John Aitken

E-Mail Website
Guest Editor
School of Environmental and Life Sciences, College of Engineering, Science and Environmental Science, University of Newcastle, Callaghan, NSW 2308, Australia
Interests: oxidative stress; antioxidants; reproductive biology; fertilization; demography
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Male infertility affects millions of individuals worldwide and remains an under-recognized contributor to reproductive failure. This Special Issue invites original research, reviews, and perspectives that explore the complex biology of sperm function and the molecular and genetic underpinnings of male infertility.

We welcome submissions that cover a broad range of topics including, but not limited to, the following:

  • Sperm development, maturation, and function.
  • Cellular and molecular mechanisms regulating spermatogenesis.
  • Sperm motility, capacitation, and acrosome reaction.
  • Oxidative stress and sperm DNA damage.
  • Epigenetics and transcriptomics in sperm biology.
  • Genetic and genomic causes of male infertility.
  • Emerging biomarkers and diagnostic tools.
  • Functional assays and models for male fertility evaluation.
  • Translational research and therapeutic strategies.

This Special Issue aims to bridge basic and clinical research, encouraging interdisciplinary approaches that advance our understanding of male reproductive health and inform better diagnostics and treatments.

Join us in advancing the field of andrology by contributing to this timely and impactful issue.

We look forward to receiving your contributions.

Dr. Mónica Vazquez-Levin
Prof. Dr. Robert John Aitken
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • human sperm
  • fertilization
  • infertility
  • biomarkers
  • genetics

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Published Papers (1 paper)

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Research

25 pages, 4295 KB  
Article
PRSS38 Is a Novel Sperm Serine Protease Involved in Human and Mouse Fertilization
by Ania Antonella Manjon, Gustavo Luis Verón, Rosario Vitale, Georgina Stegmayer, Fernanda Gonzalez Echeverria-Raffo, Lydie Lane and Mónica Hebe Vazquez-Levin
Int. J. Mol. Sci. 2025, 26(23), 11680; https://doi.org/10.3390/ijms262311680 - 2 Dec 2025
Viewed by 172
Abstract
Sperm proteases are involved in several gamete interaction events leading to fertilization. This report presents a detailed analysis of the expression and localization of serine protease PRSS38 in human and in mouse spermatozoa and its involvement in fertilization-related events, using bioinformatics, cellular, biochemical, [...] Read more.
Sperm proteases are involved in several gamete interaction events leading to fertilization. This report presents a detailed analysis of the expression and localization of serine protease PRSS38 in human and in mouse spermatozoa and its involvement in fertilization-related events, using bioinformatics, cellular, biochemical, molecular, and functional approaches. Bioinformatics analyses included genomics and data analysis, prediction of protein subcellular localization and post-translational modifications, Self-Organizing Maps (SOMs) unsupervised training with other serine proteases, protein modeling (AlphaFold), and genetic variant analysis. For cellular, biochemical, and functional studies, human semen samples were obtained from healthy normozoospermic volunteers, and cauda epididymal sperm were collected from adult Balb-c/C57 mice. PRSS38 presence was detected in human and mouse sperm protein extracts by Western immunoblotting. Sperm PRSS38 subcellular localization was determined by fluorescence immunocytochemistry. Human sperm–oocyte interaction events were assessed by means of the mouse Cumulus Penetration Assay (CPA) using mouse COCs, the Human Hemizona Assay (HZA), and the ZP-free hamster egg Sperm Penetration Assay (SPA). Mouse sperm–oocyte interactions were evaluated by means of in vitro fertilization (IVF) with COCs and denuded oocytes. PRSS38 is proposed to be a GPI-anchored serine protease (active site: His-100, Asp-150, and Ser-245) based on bioinformatics analyses. Using commercial antibodies, protein forms of the expected Mr (human: 31 kDa; mouse: 32 and 24 kDa) were specifically immunodetected in protein sperm extracts. Immunocytochemical analysis revealed a specific PRSS38 signal in the human sperm acrosomal region, equatorial segment, and flagellum. Mouse sperm PRSS38 was immunolocalized in the equatorial segment and hook. Human sperm preincubation with specific antibodies resulted in inhibition (p < 0.05) of CPA, HZA, and SPA. Mouse sperm preincubation with PRSS38 antibodies impaired (p < 0.05) homologous IVF using COCs and denuded oocytes. Genetic variants affecting residues involved in the GPI anchor and the catalytic triad were found in individuals from the general population whose PRSS38 protease function could be altered. This study provides, for the first time, an integrated analysis of PRSS38 in human and mouse sperm, contributing to our understanding of mammalian fertilization and male infertility. Full article
(This article belongs to the Special Issue The Molecular Life of Sperm: New Horizons in Male Infertility)
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