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E2F1 microdeletions and microduplications contribute to cryptorchidism, infertility and testicular tumors. Although E2f1 deletion or overexpression in mice causes spermatogenic failure, the mechanism by which E2f1 influences testicular function is unknown. This investigation revealed that E2f1-null mice develop cryptorchidism with severe gubernacular defects and progressive loss of germ cells resulting in infertility and, in rare cases, testicular tumors. It was hypothesized that germ cell depletion resulted from an increase in WNT4 levels. To test this hypothesis, the phenotype of a double-null mouse model lacking both Wnt4 and E2f1 in germ cells was analyzed. Double-null mice are fertile. This finding indicates that germ cell maintenance is dependent on E2f1 repression of Wnt4, supporting a role for Wnt4 in germ cell survival. In the future, modulation of WNT4 expression in men with cryptorchidism and spermatogenic failure due to E2F1 copy number variations may provide a novel approach to improve their spermatogenesis and perhaps their fertility potential after orchidopexy.<\/jats:p>","DOI":"10.1242\/dev.191189","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T15:31:59Z","timestamp":1610551919000},"source":"Crossref","is-referenced-by-count":23,"title":["E2F1 regulates testicular descent and controls spermatogenesis by influencing WNT4 signaling"],"prefix":"10.1242","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9203-6331","authenticated-orcid":false,"given":"Carolina J.","family":"Jorgez","sequence":"first","affiliation":[{"name":"Scott Department of Urology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Department of Surgery, Texas Children's Hospital, Houston, TX 77030, USA"},{"name":"Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Seth","sequence":"additional","affiliation":[{"name":"Scott Department of Urology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Department of Surgery, Texas Children's Hospital, Houston, TX 77030, USA"},{"name":"Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Wilken","sequence":"additional","affiliation":[{"name":"Scott Department of Urology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Bournat","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching H.","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4389-5065","authenticated-orcid":false,"given":"Dolores J.","family":"Lamb","sequence":"additional","affiliation":[{"name":"Scott Department of Urology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Brady Urology Department, Center for Reproductive Genomics and Englander Institute for Precision Medicine, Weill Cornell Medical College, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"key":"2021042701101800500_DEV191189C1","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1210\/me.2012-1016","article-title":"Direct cooperation between androgen receptor and E2F1 reveals a common regulation mechanism for androgen-responsive genes in prostate cells","volume":"26","author":"Altintas","year":"2012","journal-title":"Mol. 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