{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:10:07Z","timestamp":1783476607560,"version":"3.55.0"},"reference-count":38,"publisher":"Cambridge University Press (CUP)","issue":"2","license":[{"start":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T00:00:00Z","timestamp":1705881600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Zygote"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Spermatogenesis is a developmental process driven by interactions between germ cells and Sertoli cells. This process depends on appropriate gene expression, which might be regulated by transcription factors. This study focused on <jats:italic>Rreb1<\/jats:italic>, a zinc finger transcription factor, and explored its function and molecular mechanisms in spermatogenesis in a mouse model. Our results showed that RREB1 was predominantly expressed in the Sertoli cells of the testis. The decreased expression of RREB1 following injection of siRNA caused impaired Sertoli cell development, which was characterized using a defective blood\u2013testis barrier structure and decreased expression of Sertoli cell functional maturity markers; its essential trigger might be SMAD3 destabilization. The decreased expression of RREB1 in mature Sertoli cells influenced the cell structure and function, which resulted in abnormal spermatogenesis, manifested as oligoasthenoteratozoospermia, and we believe RREB1 plays this role by regulating the transcription of <jats:italic>Fshr<\/jats:italic> and <jats:italic>Wt1<\/jats:italic>. RREB1 has been reported to activate <jats:italic>Fshr<\/jats:italic> transcription, and we demonstrated that the knockdown of <jats:italic>Rreb1<\/jats:italic> caused a reduction in follicle-stimulating hormone receptor (FSHR) in the testis, which could be the cause of the increased sperm malformation. Furthermore, we confirmed that RREB1 directly activates <jats:italic>Wt1<\/jats:italic> promoter activity, and RREB1 downregulation induced the decreased expression of <jats:italic>Wt1<\/jats:italic> and its downstream polarity-associated genes <jats:italic>Par6b<\/jats:italic> and <jats:italic>E-cadherin<\/jats:italic>, which caused increased germ-cell death and reduced sperm number and motility. In conclusion, RREB1 is a key transcription factor essential for Sertoli cell development and function and is required for normal spermatogenesis.<\/jats:p>","DOI":"10.1017\/s0967199423000655","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T06:51:37Z","timestamp":1706165497000},"page":"130-138","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":2,"title":["Rreb1 is a key transcription factor in Sertoli cell maturation and function and spermatogenesis in mouse"],"prefix":"10.1017","volume":"32","author":[{"given":"Zhu","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longsheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meimei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0852-6894","authenticated-orcid":false,"given":"Hui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2024,1,22]]},"reference":[{"key":"S0967199423000655_ref4","doi-asserted-by":"crossref","first-page":"17071","DOI":"10.1038\/cddiscovery.2017.71","article-title":"Zinc-finger proteins in health and disease","volume":"3","author":"Cassandri","year":"2017","journal-title":"Cell Death Discovery"},{"key":"S0967199423000655_ref21","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1016\/j.ajpath.2017.07.016","article-title":"Ggnbp2-null mutation in mice leads to male infertility due to a defect at the spermiogenesis stage","volume":"187","author":"Liu","year":"2017","journal-title":"American Journal of Pathology"},{"key":"S0967199423000655_ref36","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/S0006-291X(02)00812-4","article-title":"Cross talk of two Krupple transcription factors regulates expression of the ovine FSH receptor gene","volume":"295","author":"Xing","year":"2002","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"S0967199423000655_ref3","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1098\/rstb.2009.0196","article-title":"Transcription and post-transcriptional regulation of spermatogenesis","volume":"365","author":"Bettegowda","year":"2010","journal-title":"Philosophical Transactions of the Royal Society of London. 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