Investigating the molecular mechanisms of oocyte maturation and ovulation in Nile tilapia: A focus on the steroidogenic enzyme Cyp17a2

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.