{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:46:53Z","timestamp":1791172013099,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Reproduction Devel"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>This study investigated IZUMO1, IZUMO2, and IZUMO4 expression, localization, and participation in sperm\u2010oocyte interaction, combining standard biochemical (Western immunoblotting and fluorescence immunocytochemistry) and functional (CPA, HZA, SPA) with computational biology approaches (bioinformatics, protein's 3D\u2010structure modelling). Human IZUMO1, IZUMO2, and IZUMO4 transcripts were found to be testis\u2010enriched (HPA), and expressed since puberty (MeDAS). IZUMO2 and IZUMO4 transcripts levels were lower (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) in teratozoospermic men (GEO). Human protein forms of ~40\u2009kDa (IZUMO1), ~23\u2009KDa (IZUMO2) and ~25\u2009KDa (IZUMO4) were specifically immunodetected in sperm extracts. IZUMO proteins were immunolocalized in the acrosomal region of acrosome\u2010intact and acrosome\u2010reacted cells. Sperm pre\u2010incubation with anti\u2010IZUMO antibodies resulted in lower CPA rates using anti\u2010IZUMO4 antibodies, lower HZA rates using anti\u2010IZUMO1, anti\u2010IZUMO2, or anti\u2010IZUMO4 antibodies, and lower SPA rates using anti\u2010IZUMO1 or anti\u2010IZUMO4 antibodies (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). IZUMO1 and IZUMO4 were immunodetected in mouse sperm, and antibodies also blocked homologous fertilization. Protein modeling using AlphaFold identified potential antigenic regions recognized by the antibodies used in biological assays, which impaired IZUMO1\u2010JUNO and IZUMO4\u2010JUNO protein interactions. This is the first study that reports human IZUMO1, IZUMO2, and IZUMO4 expression\/localization and involvement in gamete interaction. Findings presented enhance our understanding of the molecular interactions leading to fertilization and may contribute to male infertility diagnosis and treatment.<\/jats:p>","DOI":"10.1002\/mrd.70040","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T05:10:09Z","timestamp":1754370609000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Uncovering the Role of IZUMO Family Members in Human Fertilization"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0546-6964","authenticated-orcid":false,"given":"Ania Antonella","family":"Manjon","sequence":"first","affiliation":[{"name":"Laboratorio de Estudios de Interacci\u00f3n Celular en Reproducci\u00f3n y C\u00e1ncer. Instituto de Biolog\u00eda y Medicina Experimental (IBYME). 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E.","family":"de Raffo","sequence":"additional","affiliation":[{"name":"Centro M\u00e9dico Fertilab Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4463-6532","authenticated-orcid":false,"given":"M\u00f3nica Hebe","family":"Vazquez\u2010Levin","sequence":"additional","affiliation":[{"name":"Laboratorio de Estudios de Interacci\u00f3n Celular en Reproducci\u00f3n y C\u00e1ncer. Instituto de Biolog\u00eda y Medicina Experimental (IBYME). 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