期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 504, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2019.110694
关键词
Rapamycin; MTOR; Ovarian reserve; Primordial follicle; Oocyte developmental potential
资金
- Japan Agency for Medical Research and Development [19H03801, 18K09275, 18K19624]
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Takeda Science Foundation
- Naito Foundation
- Grants-in-Aid for Scientific Research [18K09275, 19H03801, 18K19624] Funding Source: KAKEN
The ovarian follicle pool size is limited; it decreases with age and following germ cell-damaging chemo- or radiation therapies. Due to a trend of delaying child-bearing age in the modern society, it is important to investigate the possibility to maintain the follicle reserve for middle-aged women and cancer-bearing patients subject to therapies. Earlier studies demonstrated the important role of the mammalian targets of the rapamycin (MTOR) signaling pathway in the activation of primordial follicles and suggested that treatment with the MTOR inhibitor rapamycin could maintain the follicle pool in rodents. Here, we confirmed the ability of rapamycin treatment for 3 weeks to suppress primordial follicle development and to maintain follicle pool size in mice. We further demonstrated that the developmental potential of oocytes was not affected by rapamycin treatment and the effect of rapamycin to decrease initial follicle recruitment is reversible. Using human ovarian cortical fragments grafted into immune-deficient mice, we demonstrated the ability of rapamycin to suppress follicle growth from the primordial stage. Our studies provide the basis for further studies on the possibility of using MTOR inhibitors to maintain follicle reserve in middle-aged women and cancer patients before/during germ cell-damaging therapies.
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