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Cyp17a1 (Cytochrome P450 family 17 subfamily A member 1) is thought to play essential roles in fish steroidogenesis. Therefore, to further understand its roles in steroidogenesis, sex determination, and fertility in fish, we constructed a cyp17a1 gene mutant in Nile tilapia (Oreochromis niloticus). In XX fish, mutation of the cyp17a1 gene led to a female-to-male sex reversal with a significant decline in 17\u03b2-estradiol (E2) and testosterone (T) production, and ectopic expression of male-biased markers (Dmrt1 and Gsdf) in gonads from the critical window of sex determination. Sex reversal was successfully rescued via T or E2 administration, and ovarian characteristics were maintained after termination of E2 supplementation in the absence of endogenous estrogen production in cyp17a1\u2013\/\u2013 XX fish. Likewise, deficiencies in T and 11-ketotestosterone (11-KT) production in both cyp17a1\u2013\/\u2013 XX sex-reversed males and cyp17a1\u2013\/\u2013 XY mutants resulted in meiotic initiation delays, vas deferens obstruction and sterility due to excessive apoptosis and abnormal mitochondrial morphology. However, 11-KT treatment successfully rescued the dysspermia to produce normal sperm in cyp17a1\u2013\/\u2013 male fish. Significant increases in gonadotropic hormone (gth) and gth receptors in cyp17a1\u2013\/\u2013 mutants may excessively upregulate steroidogenic gene expression in Leydig cells through a feedback loop. Taken together, our findings demonstrate that Cyp17a1 is indispensable for E2 production, which is fundamental for female sex determination and differentiation in XX tilapia. Additionally, Cyp17a1 is essential for T and 11-KT production, which further promotes spermatogenesis and fertility in XY males.<\/jats:p>","DOI":"10.1210\/endocr\/bqab205","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T14:30:36Z","timestamp":1632839436000},"source":"Crossref","is-referenced-by-count":66,"title":["Cyp17a1 is Required for Female Sex Determination and Male Fertility by Regulating Sex Steroid Biosynthesis in Fish"],"prefix":"10.1210","volume":"162","author":[{"given":"Lanying","family":"Yang","sequence":"first","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing, 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing, 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujun","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing, 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenhua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing, 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyang","family":"Miao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing, 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing, 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4967-524X","authenticated-orcid":false,"given":"Deshou","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing, 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5249-5218","authenticated-orcid":false,"given":"Linyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing, 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,9,28]]},"reference":[{"issue":"1-2","key":"2021102214335726500_CIT0001","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.mce.2009.04.009","article-title":"Endocrine\/paracrine control of zebrafish ovarian development","volume":"312","author":"Clelland","year":"2009","journal-title":"Mol Cell Endocrinol."},{"issue":"1","key":"2021102214335726500_CIT0002","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ygcen.2008.03.024","article-title":"Are we missing a mineralocorticoid in teleost fish? 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