Previous research has highlighted the significant role of progestins and glucocorticoids in fish oocyte maturation and ovulation. To clarify the molecular mechanisms underlying these processes, comprehensive investigations were conducted using a cyp17a2 mutant Nile tilapia ( Oreochromis niloticus) model. Analysis revealed pronounced Cyp17a2 expression in ovarian somatic cells of the tilapia. Female cyp17a2-deficient mutants exhibited markedly reduced levels of 17,20β-dihydroxy-4-pregnen-3-one (DHP) and cortisol/cortisone, leading to delayed meiotic initiation and impaired oocyte maturation and spawning. Notably, supplementation with human chorionic gonadotrophin (hCG), DHP, and cortisol effectively induced germinal vesicle breakdown (GVBD) and facilitated oocyte release with follicular cell layers in cyp17a2 -/- females. Additionally, cyp17a2 -/- and rescued cyp17a2 -/- females showed elevated transcription of steroidogenic enzymes involved in 17β-estradiol (E2) production compared to spawning wild-type females. Moreover, the reduction in Akt phosphorylation observed in cyp17a2-deficient females and upon inhibitor treatment impaired hCG-induced oocyte maturation. Conversely, activation of the phosphoinositide 3-kinase/protein kinase B (PI3K-Akt) signaling pathway partially rescued the oocyte maturation impairment caused by cyp17a2 mutation. Overall, these findings provide functional evidence supporting the critical role of Cyp17a2 in DHP and cortisol biosynthesis, which, in turn, facilitates oocyte maturation and ovulation through activation of the PI3K-Akt signaling pathway in fish.
脊椎动物的生殖发育过程受到类固醇激素的严格调控。早期研究表明孕激素和糖皮质激素在鱼类卵母细胞成熟和排卵等过程中起重要作用。为了深入探究这些过程的分子机制，我们在尼罗罗非鱼（ Oreochromis niloticus）中建立了类固醇合成关键基因 cyp17a2的纯合突变体。研究发现， cyp17a2突变导致雌性个体血清中孕激素（17,20β-dihydroxy-4-pregnen-3-one，DHP）和糖皮质激素（cortisol/cortisone）的水平降低，卵子发生受阻，随着鱼体的生长，卵子发生过程得到恢复，但性成熟个体的卵母细胞成熟和排卵过程受损。有趣的是，在 cyp17a2 −/−雌性个体中，外源性补充hCG、DHP和皮质醇能够诱导卵母细胞的成熟，但这些成熟的卵母细胞并没有与周围的滤泡细胞分离。与产卵后的野生雌鱼相比， cyp17a2 −/−以及激素处理的 cyp17a2 −/−雌性个体显示处更高水平的与雌激素（17β-estradiol，E2）合成相关基因的表达。此外， cyp17a2突变和抑制剂处理降低了Akt的磷酸化水平，从而减少了hCG诱导的卵母细胞成熟率。相反，激动剂处理能够部分挽救由 cyp17a2突变所导致的卵母细胞成熟损伤。总的来说，该研究为Cyp17a2在DHP和皮质醇生物合成中发挥重要作用、从而通过激活PI3K-Akt信号通路促进鱼类卵母细胞成熟和排卵这一假说提供了功能性证据。.
Keywords: Cortisol; DHP; PI3K-Akt; Reproductive process; Tilapia.