{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T19:10:17Z","timestamp":1783105817533,"version":"3.54.6"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T00:00:00Z","timestamp":1650844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFC1313003 2018YFA0107002"],"award-info":[{"award-number":["2018YFC1313003 2018YFA0107002"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31871485 82001617 81701410"],"award-info":[{"award-number":["31871485 82001617 81701410"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin City","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>The <jats:italic>SEPTIN12<\/jats:italic> gene has been associated with male infertility. Male <jats:italic>Septin12<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> chimera mice were infertile, supporting the prevailing view that <jats:italic>SEPTIN12<\/jats:italic> haploinsufficiency causes male infertility. In this study, we identified a heterozygous mutation on <jats:italic>SEPTIN12<\/jats:italic>, c.72C&amp;gt;A (p.Cys24Ter) in the male partner of a patient couple, who had a previous fertilization failure (FF) after intracytoplasmic sperm injection (ICSI) and became pregnant after ICSI together with artificial oocyte activation (AOA). To investigate the role of <jats:italic>SEPTIN12<\/jats:italic> in FF and oocyte activation, we constructed <jats:italic>Septin12<\/jats:italic> knockout mice. Surprisingly, <jats:italic>Septin12<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> male mice, but not <jats:italic>Septin12<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> male mice, are infertile, and have reduced sperm counts and abnormal sperm morphology. Importantly, AOA treatment enhances the 2-cell embryo rate of ICSI embryos injected with <jats:italic>Septin12<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> sperm, indicating that FF caused by male <jats:italic>Septin12<\/jats:italic> deficiency is overcome by AOA. Mechanistically, loss of PLC\u03b6 around the acrosome might be the reason for FF of <jats:italic>Septin12<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> sperm. Taken together, our data indicated that homozygous knockout of <jats:italic>Septin12<\/jats:italic>, but not <jats:italic>Septin12<\/jats:italic> haploinsufficiency, leads to male infertility and FF.<\/jats:p>","DOI":"10.3389\/fcell.2022.850052","type":"journal-article","created":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T10:29:35Z","timestamp":1650882575000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Homozygous Loss of Septin12, but not its Haploinsufficiency, Leads to Male Infertility and Fertilization Failure"],"prefix":"10.3389","volume":"10","author":[{"given":"Haixia","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiding","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueru","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Shuai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s12958-015-0032-1","article-title":"A Unique View on Male Infertility Around the globe","volume":"13","author":"Agarwal","year":"2015","journal-title":"Reprod. 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