{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:56:55Z","timestamp":1789829815183,"version":"4.0.1"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:00:00Z","timestamp":1722211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81901537"],"award-info":[{"award-number":["81901537"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017700","name":"the Key Technologies Research and Development Program of Henan Province","doi-asserted-by":"publisher","award":["192102310131"],"award-info":[{"award-number":["192102310131"]}],"id":[{"id":"10.13039\/501100017700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011841","name":"Xinxiang Medical University","doi-asserted-by":"publisher","award":["XYBSKYZZ201802"],"award-info":[{"award-number":["XYBSKYZZ201802"]}],"id":[{"id":"10.13039\/501100011841","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Hexokinase (HK) catalyzes the first irreversible rate-limiting step in glycolysis that converts glucose to glucose-6-phosphate. HK1 is ubiquitously expressed in the brain, erythrocytes, and other tissues where glycolysis serves as the major source of ATP production. Spermatogenic cell-specific type 1 hexokinase (HK1S) is expressed in sperm but its physiological role in male mice is still unknown. In this study, we generate <jats:italic>Hk1s<\/jats:italic> knockout mice using the CRISPR\/Cas9 system to study the gene function <jats:italic>in vivo<\/jats:italic>. <jats:italic>Hk1s<\/jats:italic> mRNA is exclusively expressed in testes starting from postnatal day 18 and continuing to adulthood. HK1S protein is specifically localized in the outer surface of the sperm fibrous sheath (FS). Depletion of <jats:italic>Hk1s<\/jats:italic> leads to infertility in male mice and reduces sperm glycolytic pathway activity, yet they have normal motile parameters and ATP levels. In addition, by using <jats:italic>in vitro<\/jats:italic> fertilization (IVF), <jats:italic>Hk1s<\/jats:italic> deficient sperms are unable to fertilize cumulus-intact or cumulus-free oocytes, but can normally fertilize zona pellucida-free oocytes. Moreover, <jats:italic>Hk1s<\/jats:italic> deficiency impairs sperm migration into the oviduct, reduces acrosome reaction, and prevents capacitation-associated increases in tyrosine phosphorylation, which are probable causes of infertility. Taken together, our results reveal that HK1S plays a critical role in sperm function and male fertility in mice.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011357","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T17:53:14Z","timestamp":1722275594000},"page":"e1011357","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Spermatogenic cell-specific type 1 hexokinase (HK1S) is essential for capacitation-associated increase in tyrosine phosphorylation and male fertility in mice"],"prefix":"10.1371","volume":"20","author":[{"given":"Yingchao","family":"Tian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinshui","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuntai","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9056-0604","authenticated-orcid":true,"given":"Yongjie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0468-0589","authenticated-orcid":true,"given":"Yushan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,7,29]]},"reference":[{"issue":"4612","key":"pgen.1011357.ref001","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/181851a0","article-title":"Capacitation of mammalian spermatozoa","volume":"181","author":"CR Austin","year":"1958","journal-title":"Nature"},{"key":"pgen.1011357.ref002","doi-asserted-by":"crossref","first-page":"102176","DOI":"10.1016\/j.redox.2021.102176","article-title":"Increased mitochondrial activity upon CatSper channel activation is required for mouse sperm capacitation","volume":"48","author":"JJ Ferreira","year":"2021","journal-title":"Redox Biol"},{"issue":"22","key":"pgen.1011357.ref003","doi-asserted-by":"crossref","first-page":"4471","DOI":"10.1242\/dev.090613","article-title":"The cell biology of mammalian fertilization","volume":"140","author":"M. 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