Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool

• 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.

Keyword

1-Phosphatidylinositol 3-Kinase/metabolism

Animals

Female

Follicular Atresia

Mice

Mice; Transgenic

Oocytes/cytology/growth & development/*physiology

Organ Size

Ovarian Failure; Premature/physiopathology

Ovarian Follicle/cytology/*physiology

Ovary/anatomy & histology/physiology

Ovulation

PTEN Phosphohydrolase/genetics/*physiology

Phosphorylation

Protein Kinases/metabolism

Ribosomal Protein S6/metabolism

Signal Transduction

Publication and Content Type

ref (subject category)

art (subject category)