{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T20:30:59Z","timestamp":1792873859574,"version":"4.5.0"},"reference-count":120,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Conventional semen analysis fails to capture the molecular determinants underlying impaired reproductive function. Emerging evidence positions seminal plasma (SP) and extracellular vesicles (EVs) as dynamic regulators of sperm physiology, rather than passive transport components. SP, enriched with proteins, metabolites, hormones, and antioxidants, modulates sperm motility, capacitation, acrosome reaction, and immune tolerance. Complementarily, EVs, including prostasomes, epididymosomes, and testicular vesicles, deliver proteins, lipids, and small RNAs that remodel sperm membranes, protect against oxidative insults, and influence fertilization success. A critical dimension of the SP-EV axis is its role in balancing oxidative stress (OS) and endocrine signaling. Hormones and metabolic regulators within SP, together with EV-mediated transfer of receptors and regulatory RNAs, further integrate systemic metabolic health with local reproductive outcomes. Dysregulation of these networks, particularly in conditions such as varicocele, obesity, diabetes, and idiopathic infertility, compromises sperm function and reduces assisted reproductive technology (ART) success. This evidence-based review synthesizes current evidence on SP and EVs as \u2018molecular gatekeepers\u2019 in male infertility, emphasizing OS regulation, endocrine crosstalk, and their potential as biomarker reservoirs. By integrating proteomic, metabolomic, and transcriptomic insights, the translational opportunities for biomarker-informed diagnostics, prognostication, and therapeutic interventions are highlighted.<\/jats:p>","DOI":"10.3390\/cimb48010117","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T09:16:59Z","timestamp":1769159819000},"page":"117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Seminal Plasma and Extracellular Vesicles as Molecular Gatekeepers: Oxidative Stress, Endocrine Crosstalk, and Biomarker Discovery in Male Infertility"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1928-5048","authenticated-orcid":false,"given":"Pallav","family":"Sengupta","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine, Gulf Medical University, Ajman 4184, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7893-5282","authenticated-orcid":false,"given":"Sulagna","family":"Dutta","sequence":"additional","affiliation":[{"name":"Basic Medical Sciences Department, College of Medicine, Ajman University, Ajman 3464, United Arab Emirates"},{"name":"Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman 3464, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8128-054X","authenticated-orcid":false,"given":"Mahir Khalil","family":"Jallo","sequence":"additional","affiliation":[{"name":"Center of Internal Medicine & Endocrinology, Thumbay University Hospital, Ajman 4184, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2765-6176","authenticated-orcid":false,"given":"Israel Maldonado","family":"Rosas","sequence":"additional","affiliation":[{"name":"Citmer Reproductive Medicine, Mexico City 11520, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4174-1852","authenticated-orcid":false,"given":"Shubhadeep","family":"Roychoudhury","sequence":"additional","affiliation":[{"name":"Department of Life Science and Bioinformatics, Assam University, Silchar 788011, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Huang, B., Wang, Z., Kong, Y., Jin, M., and Ma, L. 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