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A putative mitotic checkpoint dependent on mTOR function controls cell proliferation and survival in ovarian

Aylin Yaba1, Veronica Bianchi, Andrea Borini

  • 1Department of Obstetrics, Gynecology, & Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut 06510, SA.

Reproductive Sciences (Thousand Oaks, Calif.)
|February 16, 2008
PubMed

Insights

Mammalian target of rapamycin (mTOR) regulates ovarian cell growth. Inhibiting mTOR reduces granulosa cell proliferation and follicle growth, suggesting nutrient and stress signals directly impact ovarian follicle development.

Area of Science:

  • Reproductive Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Target of rapamycin (TOR) proteins are crucial for nutrient sensing and cell growth regulation.
  • Mammalian TOR (mTOR) is a key signaling protein involved in cellular processes like growth, survival, and metabolism.

Purpose of the Study:

  • To investigate the expression and role of mammalian TOR (mTOR) and its cofactors (Raptor, Rictor, LST8) in the mouse ovary.
  • To determine the effect of mTOR inhibition on granulosa cell proliferation and follicle growth in vitro.

Main Methods:

  • Immunohistochemical analysis of mTOR and its cofactors in mouse ovarian tissues.
  • In vitro culture of ovarian follicles with varying concentrations of rapamycin (mTOR inhibitor).
  • Assessment of granulosa cell proliferation and follicle growth rates.

Main Results:

  • mTOR exhibited high cytoplasmic/perinuclear expression in granulosa cells.
  • The active, phosphorylated form of mTOR (P-mTOR) was abundant during M-phase, localized to the mitotic spindle and contractile ring.
  • Rapamycin treatment dose-dependently reduced granulosa cell proliferation and follicle growth.
  • mTOR inhibition prevented follicle atresia.

Conclusions:

  • mTOR signaling is essential for normal granulosa cell proliferation and ovarian follicle growth.
  • The findings support a model where nutrient and stress signals, mediated by mTOR, directly influence ovarian follicle development and survival.

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