Cyp17a1 is required for female sex determination and male fertility by regulating sex steroid biosynthesis in fish
Cyp17a1 is required for female sex determination and male fertility by regulating sex steroid biosynthesis in fish
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Cyp17a1 通过调节鱼类的性类固醇生物合成来实现雌性性别决定和雄性生育能力
DOI：
10.1210/endocr/bqab205
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发表时间：
2021
期刊：
影响因子：
4.8
通讯作者：
Zhou Linyan
中科院分区：
文献类型：
--
作者：
Yang Lanying;Zhang Xuefeng;Liu Shujun;Zhao Chenhua;Miao Yiyang;Jin Li;Wang Deshou;Zhou Linyan
In teleost fish, sex steroids are involved in sex determination, sex differentiation, and fertility. Particularly, 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 cyp17a1 gene led to a female-to-male sex reversal with a significant decline in 17β-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 -/--XX fish. Likewise, deficiencies in T and 11-KT production in both cyp17a1 -/--XX sex reversed males and cyp17a1 -/--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 -/- male fish. Significant increases in fshβ, lhβ, and gth receptors in cyp17a1 -/- 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.
