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Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a.

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.

Pubmed ID: 12855809


  • Castrillon DH
  • Miao L
  • Kollipara R
  • Horner JW
  • DePinho RA


Science (New York, N.Y.)

Publication Data

July 11, 2003

Associated Grants

  • Agency: PHS HHS, Id: K08

Mesh Terms

  • Animals
  • Apoptosis
  • Cell Size
  • DNA-Binding Proteins
  • Female
  • Follicle Stimulating Hormone
  • Follicular Atresia
  • Forkhead Transcription Factors
  • Gene Targeting
  • Granulosa Cells
  • Humans
  • Infertility, Female
  • Luteinizing Hormone
  • Male
  • Mice
  • Mice, Knockout
  • Oocytes
  • Ovarian Follicle
  • Ovary
  • Ovulation
  • Primary Ovarian Insufficiency
  • Sexual Maturation
  • Superovulation
  • Transcription Factors