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Science 301 (5630): 215-218

Copyright © 2003 by the American Association for the Advancement of Science

Suppression of Ovarian Follicle Activation in Mice by the Transcription Factor Foxo3a

Diego H. Castrillon,1,2* Lili Miao,1 Ramya Kollipara,1 James W. Horner,1 Ronald A. DePinho1{dagger}

Abstract: Foxo transcription factors have been implicated in diverse biological processes, including metabolism, cellular stress responses, and aging. Here, we show that Foxo3a–/– female mice exhibit a distinctive ovarian phenotype of global follicular activation leading to oocyte death, early depletion of functional ovarian follicles, and secondary infertility. Foxo3a thus functions at the earliest stages of follicular growth as a suppressor of follicular activation. In addition to providing a molecular entry point for studying the regulation of follicular growth, these results raise the possibility that accelerated follicular initiation plays a role in premature ovarian failure, a common cause of infertility and premature aging in women.

1 Department of Medical Oncology, Dana-Farber Cancer Institute, and Departments of Medicine and Genetics, Harvard Medical School, Boston, MA 02115, USA. 2 Women's and Perinatal Pathology Division, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

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* Present address: Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical School, Dallas, TX 75390, USA.

{dagger} To whom correspondence should be addressed: E-mail: ron_depinho{at}

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Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development.
M. Uda, C. Ottolenghi, L. Crisponi, J. E. Garcia, M. Deiana, W. Kimber, A. Forabosco, A. Cao, D. Schlessinger, and G. Pilia (2004)
Hum. Mol. Genet. 13, 1171-1181
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Methods for quantifying follicular numbers within the mouse ovary.
M Myers, K L Britt, N G M Wreford, F J P Ebling, and J B Kerr (2004)
Reproduction 127, 569-580
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Androgens Negatively Regulate Forkhead Transcription Factor FKHR (FOXO1) through a Proteolytic Mechanism in Prostate Cancer Cells.
H. Huang, D. C. Muddiman, and D. J. Tindall (2004)
J. Biol. Chem. 279, 13866-13877
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