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A Putative Mitotic Checkpoint Dependent on mTOR Function Controls Cell Proliferation and Survival in Ovarian Granulosa Cells

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Abstract

The conserved target of rapamycin (TOR) proteins are involved in sensing nutrient levels and/or stress and the resultant control of cell growth, size, and survival. The authors assess mammalian TOR (mTOR) kinase expression in the mouse ovary and also the expression of its cofactors, Raptor, Rictor, and LST8. In granulosa cells, mTOR demonstrates high cytoplasmic/perinuclear expression. The kinase-active serine 2448—phosphorylated form of mTOR (P-mTOR) is present at very high levels during the M-phase. P-mTOR was enriched on or near the mitotic spindle and also near the contractile ring during cytokinesis. Rapamycin inhibition of mTOR resulted in both reduced granulosa cell proliferation and reduced follicle growth in vitro, each in a dose-dependent fashion. Follicles cultured in rapamycin did not undergo atresia. mTOR inhibition results in a reduction in granulosa cell proliferation, supporting a model in which stress and nutritional cues may directly influence ovarian follicle growth.

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Authors and Affiliations

  1. Department of Obstetrics, Gynecology, & Reproductive Sciences, Yale School of Medicine, 300 George Street, Room 770D, New Haven, Connecticut, 06510, USA

    Aylin Yaba MSc, Veronica Bianchi PhD & Joshua Johnson PhD

  2. Tecnobios Procreazione, Bologna, Italy

    Veronica Bianchi PhD & Andrea Borini MD

Authors
  1. Aylin Yaba MSc
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  2. Veronica Bianchi PhD
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  3. Andrea Borini MD
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  4. Joshua Johnson PhD
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Corresponding author

Correspondence to Joshua Johnson PhD.

Additional information

We would like to thank Dr John S. Davis for commentary on the article prior to submission. Dr Vikki M. Abrahams provided invaluable assistance with cell viability assessment. Jimmy Hom and Brett Carisio are also thanked for enthusiastic, helpful technical assistance.

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Yaba, A., Bianchi, V., Borini, A. et al. A Putative Mitotic Checkpoint Dependent on mTOR Function Controls Cell Proliferation and Survival in Ovarian Granulosa Cells. Reprod. Sci. 15, 128–138 (2008). https://doi.org/10.1177/1933719107312037

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  • DOI: https://doi.org/10.1177/1933719107312037

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