Cell Autonomous Phosphoinositide 3-Kinase Activation in Oocytes Disrupts Normal Ovarian Function Through Promoting Survival and Overgrowth of Ovarian Follicles

摘要: In this study, we explored the effects of oocytic phosphoinositide 3-kinase (PI3K) activation on folliculogensis by generating transgenic mice, in which oocyte-specific Cre-recombinase induces expression constitutively active mutant PI3K during formation primordial follicles. The ovaries neonatal (Cre+) mice showed significantly reduced apoptosis follicles, resulted an excess number follicles per ovary. Thus, elevation phosphatidylinositol (3,4,5)-trisphosphate levels within oocytes promotes survival development. Despite increase AKT phosphorylation, Cre+ remained dormant demonstrating a nuclear accumulation phosphatase and tensin homolog deleted chromosome 10 (PTEN). These containing high level PTEN persisted postpubertal females, suggesting that is dominant factor maintenance female reproductive lifespan through regulation follicle recruitment. Although activity were elevated, subsequent antral with developmentally competent progressed normally prepubertal mice. However, mature anovulatory. Because postnatal day 50 released cumulus-oocyte complexes response to super-ovulation treatment, anovulatory phenotype was not due follicular defects but rather endocrine abnormalities, likely caused overgrown Our current study has elucidated critical role function, as well presence PTEN-mediated mechanism prevention immature activation.