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.
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.
Gen Comp Endocrinol. 2021 Nov 1;313:113893. doi: 10.1016/j.ygcen.2021.113893. Epub 2021 Aug 27.
The involvement of sex steroids in sex determination and differentiation is relatively conserved among non-mammalian vertebrates, especially in fish. Thanks to the advances in genome sequencing and genome editing, significant progresses have been made in the understanding of steroidogenic pathway and hormonal regulation of sex determination and differentiation in fish. It seems that loss of function study of single gene challenges the traditional views that estrogen is required for ovarian differentiation and androgen is needed for testicular development, but it is not so in essence. Steroidogenic enzymes can be classified into two categories based on expression and enzyme activities in fish. One type, encoded by star2, cyp17a1 and cyp19a1a, is involved in estrogen production and exclusively expressed in the gonads. Mutation of these genes results in the up-regulation of male pathway genes and sex reversal from genetic female to male. The other type, encoded by the duplicated paralogs of the above genes, including star1, cyp11a1, cyp17a2 and cyp19a1b, as well as cyp11c1 gene, is dominantly expressed both in gonads and extra-gonadal tissues. Mutation of these genes alters the steroids (androgen, DHP and cortisol) production and spermatogenesis, fertility, secondary sexual characteristics and sexual behavior, but usually does not affect the sex differentiation. For the estrogen receptors (esr1, esr2a and esr2b), single mutation failed to, but double and triple mutation leads to sex reversal from female to male, indicating that at least Esr2a and Esr2b are required to mediate the role of estrogen in sex determination proved by gene editing experiments. Taken together, results from gene editing enrich our understanding of steroid synthesis pathways and further confirm the critical role of estrogen in female sex determination by antagonizing the male pathway in fish.
性类固醇在性别决定和分化中的作用在非哺乳动物脊椎动物中相对保守，尤其是在鱼类中。由于基因组测序和基因组编辑技术的进步，人们在理解鱼类类固醇生成途径和激素对性别决定和分化的调控方面取得了重大进展。似乎单个基因的功能丧失研究挑战了雌激素是卵巢分化所必需的，雄激素是睾丸发育所必需的传统观点，但从本质上讲并非如此。类固醇生成酶可以根据鱼类中的表达和酶活性分为两类。一类由 star2、cyp17a1 和 cyp19a1a 编码，参与雌激素的产生，仅在性腺中表达。这些基因的突变导致雄性途径基因的上调和遗传雌性向雄性的性反转。另一类由上述基因的重复等位基因（包括 star1、cyp11a1、cyp17a2 和 cyp19a1b 以及 cyp11c1 基因）编码，在性腺和性腺外组织中均显性表达。这些基因的突变改变了类固醇（雄激素、DHP 和皮质醇）的产生和精子发生、生育能力、第二性征和性行为，但通常不影响性别分化。对于雌激素受体（esr1、esr2a 和 esr2b），单个突变未能导致性反转，但双突变和三突变导致从雌性到雄性的性反转，表明至少 Esr2a 和 Esr2b 是介导基因编辑实验证实的雌激素在鱼类性别决定中的作用所必需的。总之，基因编辑的结果丰富了我们对类固醇合成途径的理解，并进一步证实了雌激素通过拮抗鱼类雄性途径在雌性性别决定中的关键作用。
