| In the mammalian ovary, primordial follicles are generated early in life andremain dormant for prolonged periods. Their growth resumes via primordial follicleactivation, and then continue to grow until the preovulatory stage under theregulation of hormones and growth factors, such as estrogen, follicle stimulatinghormone (FSH), and insulin-like growth factor-I (IGF-I). Both FSH and IGF-Iactivate the PI3K/Akt signaling pathway in granulosa cells (GCs), yet it remainsinconclusive whether PI3K pathway is crucial for follicle growth. In this study, wehave investigated the p110delta-isoform (encoded for by the Pik3cd gene) of thePI3K catalytic subunit expression in the mouse ovary and its function in fertility.Pik3cd null females were subfertile, had fewer growing follicles and more atreticantral follicles in the ovary and responded poorly to exogenous gonadotropins whencompared to controls. Ovary transplantation assay showed Pik3cd null ovariesresponded poorly to FSH stimulation in-vitro, which confirmed the follicle growthdefect was intrinsically ovarian. In addition, estradiol (E2)-stimulated follicle growthand GC proliferation in preantral follicles were impaired in Pik3cd null ovaries. FSHand E2substantially activated the PI3K/Akt pathway in GCs of control mice, but notin those of Pik3cd null mice. However, primordial follicle activation and oocytemeiotic maturation were not affected by Pik3cd knockout. Thus, thep110delta-isoform of the PI3K catalytic subunit is a key component of the PI3K pathway for both FSH and E2-stimulated follicle growth in ovarian granulosa cells,but is not required for primordial follicle activation and oocyte development. |
