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.

性类固醇参与性别决定和分化在非哺乳动物脊椎动物中相对保守，特别是在鱼类中。由于基因组测序和基因组编辑的进步，在对鱼类性别决定和分化的类固醇生成途径和激素调节的理解方面取得了重大进展。单基因功能丧失研究似乎挑战了卵巢分化需要雌激素、睾丸发育需要雄激素的传统观点，但实质并非如此。根据在鱼类中的表达和酶活性，类固醇生成酶可分为两类。一种类型，由star2、cyp17a1和cyp19a1a编码，参与雌激素的产生并仅在性腺中表达。这些基因的突变导致男性通路基因的上调和从遗传女性到男性的性别逆转。另一种类型，由上述基因的重复旁系同源物编码，包括star1、cyp11a1、cyp17a2和cyp19a1b，以及cyp11c1基因，主要在性腺和性腺外组织中表达。这些基因的突变会改变类固醇（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，但通常不会影响性别分化。对于雌激素受体 ( esr1 , esr2a和esr2b），单突变失败，但双突变和三突变导致从女性到男性的性别逆转，表明基因编辑实验证明至少需要 Esr2a 和 Esr2b 来介导雌激素在性别决定中的作用。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，并通过拮抗鱼类的雄性途径进一步证实了雌激素在雌性性别决定中的关键作用。