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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis
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Cell Size
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Female
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Follicle Stimulating Hormone / blood
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Follicular Atresia
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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Gene Targeting
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Granulosa Cells / cytology
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Granulosa Cells / physiology
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Humans
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Infertility, Female
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Luteinizing Hormone / blood
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Male
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Mice
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Mice, Knockout
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Oocytes / cytology
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Oocytes / physiology
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Ovarian Follicle / growth & development
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Ovarian Follicle / physiology*
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Ovary / metabolism
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Ovulation
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Primary Ovarian Insufficiency / etiology
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Sexual Maturation
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Superovulation
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Transcription Factors / genetics
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Transcription Factors / physiology*
Substances
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DNA-Binding Proteins
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FOXO1 protein, human
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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Transcription Factors
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Luteinizing Hormone
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Follicle Stimulating Hormone