Rapamycin preserves the follicle pool reserve and prolongs the ovarian lifespan of female rats via modulating mTOR activation and sirtuin expression |
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Authors: | Xing-mei Zhang Li Li Jin-jie Xu Na Wang Wei-juan Liu Xuan-hao Lin Yu-cai Fu Li-li Luo |
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Affiliation: | 1. Department of Gynaecology and Obstetrics of the First Affiliated Hospital, Medical College, Shantou University, Shantou, 515041, China;2. Laboratory of Cell Senescence, Medical College, Shantou University, Shantou, 515041, China;3. Department of Pathology of Shantou Central Hospital, Shantou, 515041, China |
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Abstract: | To maintain the normal length of female reproductive life, the majority of primordial follicles must be maintained in a quiescent state for later use. In this study, we aimed to study the effects of rapamycin on primordial follicle development and investigate the role of mTOR and sirtuin signaling. Rats were treated every other day with an intraperitoneal injection of rapamycin (5 mg/kg) or vehicle. After 10 weeks of treatment, ovaries were harvested for hematoxylin and eosin (HE) staining, and analysis by immunohistochemistry and Western blotting. HE staining showed that the number and percentage of primordial follicles in the rapamycin-treated group were twice the control group (P < 0.001). Immunohistochemical analysis showed that mTOR and phosphorylated-p70S6K were extensively expressed in surviving follicles with strong staining observed in the cytoplasm of the oocyte. Western blotting showed decreased expression of phosphorylated mTOR and phosphorylated p70S6K in the rapamycin-treated group, and increased the expression of both SIRT1 and SIRT6 compared to the control group (P < 0.05). Taken together, these results suggest that rapamycin may inhibit the transition from primordial to developing follicles and preserve the follicle pool reserve, thus extending the ovarian lifespan of female rats via the modulation of mTOR and sirtuin signalings. |
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Keywords: | P70S6K, ribosomal protein S6 kinase mTOR, the mammalian target of rapamycin SIRT, silent information regulator Tsc, tuberous sclerosis complex mTORC1, the mammalian target of rapamycin complex 1 POF, premature ovarian failure PTEN, phosphatase and tensin homolog deleted on chromosome 10 FRAP, FK506 binding protein 12-rapamycin associated protein S6K1, S6 kinase 1 rpS6, ribosomal protein S6 CR, calorie restriction CL, corpora lutea |
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