mTORC1 Signaling in Oocytes Is Dispensable for the Survival of Primordial Follicles and for Female FertilityReport as inadecuate




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The molecular mechanisms underlying reproductive aging and menopausal age in female mammals are poorly understood. Mechanistic target of rapamycin complex 1 mTORC1 is a central controller of cell growth and proliferation. To determine whether mTORC1 signaling in oocytes plays a direct role in physiological follicular development and fertility in female mice, we conditionally deleted the specific and essential mTORC1 component Rptor regulatory-associated protein of mTORC1 from the oocytes of primordial follicles by using transgenic mice expressing growth differentiation factor 9 Gdf-9 promoter-mediated Cre recombinase. We provide in vivo evidence that deletion of Rptor in the oocytes of both primordial and further-developed follicles leads to the loss of mTORC1 signaling in oocytes as indicated by loss of phosphorylation of S6K1 and 4e-bp1 at T389 and S65, respectively. However, the follicular development and fertility of mice lacking Rptor in oocytes were not affected. Mechanistically, the loss of mTORC1 signaling in Rptor-deleted mouse oocytes led to the elevation of phosphatidylinositol 3-kinase PI3K signaling that maintained normal follicular development and fertility. Therefore, this study shows that loss of mTORC1 signaling in oocytes triggers a compensatory activation of the PI3K signaling cascade that maintains normal ovarian follicular development and fertility.



Author: Nagaraju Gorre , Deepak Adhikari, Rebecca Lindkvist, Mats Brännström, Kui Liu, Yan Shen

Source: http://plos.srce.hr/



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