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To study the importance of NR5A1 during early gonadal sex differentiation, we generated <jats:italic>Sox9-Cre<\/jats:italic>-<jats:italic>Nr5a1<\/jats:italic> conditional knockout (cKO) mice: <jats:italic>Sox9-Cre;Nr5a1<\/jats:italic><jats:sup><jats:italic>flox\/flox<\/jats:italic><\/jats:sup> and <jats:italic>Sox9-Cre;Nr5a1<\/jats:italic><jats:sup><jats:italic>flox\/\u2212<\/jats:italic><\/jats:sup> mice. Double-immunostaining for NR5A1 and AMH revealed silenced NR5A1 in Sertoli cells and reduced AMH<jats:sup>+<\/jats:sup> cells in the gonads of XY <jats:italic>Sox9-Cre<\/jats:italic>-<jats:italic>Nr5a1<\/jats:italic> cKO mice between embryonic days 12.5 (E12.5) and E14.5. Double-immunostaining for SOX9 and FOXL2 further indicated an early block in Sertoli cells and ectopic granulosa cell differentiation. The number of cells expressing the Leydig cell marker 3\u03b2HSD obviously reduced in the gonads of XY <jats:italic>Sox9-Cre;Nr5a1<\/jats:italic><jats:sup><jats:italic>flox\/\u2212<\/jats:italic><\/jats:sup> but not <jats:italic>Sox9-Cre;Nr5a1<\/jats:italic><jats:sup><jats:italic>flox\/flox<\/jats:italic><\/jats:sup> mice at E15.5. The presence of STRA8<jats:sup>+<\/jats:sup> cells indicated that germ cells entered meiosis in the gonads of XY <jats:italic>Sox9-Cre<\/jats:italic>-<jats:italic>Nr5a1<\/jats:italic> cKO mice. The results of qRT-PCR revealed remarkably reduced and elevated levels of testis and ovary markers, respectively, in the gonads of XY <jats:italic>Sox9-Cre<\/jats:italic>-<jats:italic>Nr5a1<\/jats:italic> cKO mice at E12.5\u2012E13.5. These data suggested that the loss of <jats:italic>Nr5a1<\/jats:italic> abrogates the testicular pathway and induces the ectopic ovarian pathway, resulting in postnatal partial\/complete male-to-female gonadal sex reversal. Our findings provide evidence for the critical role of NR5A1 in murine gonadal sex determination in vivo.<\/jats:p>","DOI":"10.1038\/s41598-021-84095-y","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T11:03:35Z","timestamp":1614164615000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The conditional deletion of steroidogenic factor 1 (Nr5a1) in Sox9-Cre mice compromises testis differentiation"],"prefix":"10.1038","volume":"11","author":[{"given":"Yayoi","family":"Ikeda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Tagami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamiko","family":"Maekawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"84095_CR1","doi-asserted-by":"publisher","first-page":"2409","DOI":"10.1101\/gad.228080.113","volume":"27","author":"T Svingen","year":"2013","unstructured":"Svingen, T. & Koopman, P. 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