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Science 319 (5863): 611-613

Copyright © 2008 by the American Association for the Advancement of Science

Oocyte-Specific Deletion of Pten Causes Premature Activation of the Primordial Follicle Pool

Pradeep Reddy,1 Lian Liu,1,2* Deepak Adhikari,1* Krishna Jagarlamudi,1* Singareddy Rajareddy,1* Yan Shen,1 Chun Du,1 Wenli Tang,1 Tuula Hämäläinen,3 Stanford L. Peng,4 Zi-Jian Lan,5 Austin J. Cooney,6 Ilpo Huhtaniemi,3,7 Kui Liu1{dagger}

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.

1 Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.
2 Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China.
3 Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.
4 Clinical Research and Exploratory Development, Roche Palo Alto, Palo Alto, CA 94304, USA.
5 Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.
6 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
7 Department of Reproductive Biology, Imperial College London, Hammersmith Campus, London W12 0NN, UK.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: kui.liu{at}medchem.umu.se


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