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.
Reddy
Pradeep
P
Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.
Liu
Lian
L
Adhikari
Deepak
D
Jagarlamudi
Krishna
K
Rajareddy
Singareddy
S
Shen
Yan
Y
Du
Chun
C
Tang
Wenli
W
Hämäläinen
Tuula
T
Peng
Stanford L
SL
Lan
Zi-Jian
ZJ
Cooney
Austin J
AJ
Huhtaniemi
Ilpo
I
Liu
Kui
K
D000818:Animals; D005260:Female; D005496:Follicular Atresia; D051379:Mice; D008822:Mice, Transgenic; D009865:Oocytes / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D009929:Organ Size; D006080:Ovarian Follicle / Q000166:cytology / Q000502:physiology*; D010053:Ovary / Q000033:anatomy & histology / Q000502:physiology; D010060:Ovulation; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D016649:Primary Ovarian Insufficiency / Q000503:physiopathology; D011494:Protein Kinases / Q000378:metabolism; D038601:Ribosomal Protein S6 / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D038601:Ribosomal Protein S6; D058570:TOR Serine-Threonine Kinases; C546843:mTOR protein, mouse; C487757:Pten protein, mouse