Oocyte-Specific Deletion of <i>Pten</i> Causes Premature Activation of the Primordial Follicle Pool

TLDR

In mammals, primordial follicles are progressively activated from a dormant pool, and menopause occurs when this pool is exhausted, yet the molecular mechanisms controlling activation remain poorly understood. Deletion of PTEN in mouse oocytes activates the entire primordial follicle pool, rapidly depleting it and causing premature ovarian failure, demonstrating that the oocyte PTEN‑PI3K pathway regulates follicle activation.

Abstract

In the mammalian ovary, progressive activation of primordial follicles from the dormant pool serves as the source of fertilizable ova. Menopause, or the end of female reproductive life, occurs when the primordial follicle pool is exhausted. However, the molecular mechanisms underlying follicle activation are poorly understood. We provide genetic evidence that in mice lacking PTEN (phosphatase and tensin homolog deleted on chromosome 10) in oocytes, a major negative regulator of phosphatidylinositol 3-kinase (PI3K), the entire primordial follicle pool becomes activated. Subsequently, all primordial follicles become depleted in early adulthood, causing premature ovarian failure (POF). Our results show that the mammalian oocyte serves as the headquarters of programming of follicle activation and that the oocyte PTEN-PI3K pathway governs follicle activation through control of initiation of oocyte growth.