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Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a
Diego H Castrillon1, Lili Miao, Ramya Kollipara
1Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
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.
Insights
Foxo3a deficiency in female mice causes ovarian follicular activation, leading to infertility. This suggests Foxo3a suppresses early follicular growth, and its loss may contribute to premature ovarian failure.
Area of Science:
- Reproductive biology
- Molecular genetics
- Endocrinology
Background:
- Foxo transcription factors regulate critical cellular processes like metabolism, stress response, and aging.
- The role of Foxo transcription factors in ovarian biology remains largely unexplored.
Purpose of the Study:
- To investigate the function of Foxo3a in ovarian follicle development and female fertility.
- To determine the consequences of Foxo3a deficiency on ovarian follicle dynamics.
Main Methods:
- Generation and analysis of Foxo3a knockout (Foxo3a-/-) female mice.
- Histological examination of ovarian tissues to assess follicular status.
- Evaluation of fertility and ovarian follicle depletion.
Main Results:
- Foxo3a-/- female mice displayed a unique ovarian phenotype characterized by global follicular activation.
- This activation resulted in oocyte death and premature depletion of functional ovarian follicles.
- Foxo3a-/- mice exhibited secondary infertility.
Conclusions:
- Foxo3a acts as a crucial suppressor of follicular activation during the early stages of follicular growth.
- The findings suggest that accelerated follicular initiation due to Foxo3a loss may contribute to premature ovarian failure.
- This study provides a molecular target for understanding infertility and premature aging in women.
