Shuang Wu1, Yining Wang1, Haixiang Ding1, Ningxia Sun1, Yan Liu1, Liang Wang1, Fei Sheng1, Honghong Zhang1, Fu Yang2, Wen Li3. 1. Department of Reproductive Medicine Center, Changzheng Hospital, Second Military Medical University, Shanghai, China. 2. Department of Medical Genetics, Second Military Medical University, Shanghai, China. 3. Shanghai Key Laboratory of Embryo Original Diseases, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Abstract
BACKGROUND: Premature ovarian insufficiency (POI) is characterized by abnormal ovarian function before the age of 40. POI showed that primordial follicles developed in disorder. mTOR signaling plays a vital role in the process of follicle development. It has been verified that the mTOR signaling pathway activator, MHY1485, can promote primordial follicle development in mice. We considered that MHY1485 would be a promising fertility preservation method for POI patients. METHODS: The fragmented ovarian tissues of normal woman was cultured with activator MHY1485 in vitro, and then the control and activated ovaries were transplanted into the kidney capsules of ovariectomized mice. We then used the Infinium Human Methylation EPIC BeadChip to verify the DNA methylation level of ovarian tissues, thus exploring the effectiveness of them. RESULTS: MHY1485 stimulated mTOR, S6K1, and rpS6 phosphorylation. Cultured with MHY1485, ovarian weights increased and endocrine function was restored. The number of growing follicles was increased. The in vitro activation process did not induce histological changes or abnormal DNA methylation occurrence. CONCLUSION: MHY1485 for in vitro activation (IVA) is effective for ovarian rejuvenation and is a potential therapeutic treatment for POI patients.
BACKGROUND: Premature ovarian insufficiency (POI) is characterized by abnormal ovarian function before the age of 40. POI showed that primordial follicles developed in disorder. mTOR signaling plays a vital role in the process of follicle development. It has been verified that the mTOR signaling pathway activator, MHY1485, can promote primordial follicle development in mice. We considered that MHY1485 would be a promising fertility preservation method for POI patients. METHODS: The fragmented ovarian tissues of normal woman was cultured with activator MHY1485 in vitro, and then the control and activated ovaries were transplanted into the kidney capsules of ovariectomized mice. We then used the Infinium Human Methylation EPIC BeadChip to verify the DNA methylation level of ovarian tissues, thus exploring the effectiveness of them. RESULTS: MHY1485 stimulated mTOR, S6K1, and rpS6 phosphorylation. Cultured with MHY1485, ovarian weights increased and endocrine function was restored. The number of growing follicles was increased. The in vitro activation process did not induce histological changes or abnormal DNA methylation occurrence. CONCLUSION: MHY1485 for in vitro activation (IVA) is effective for ovarian rejuvenation and is a potential therapeutic treatment for POI patients.