The Efficacy and Safety of the mTOR Signaling Pathway Activator, MHY1485, for Activation of Human Ovarian Tissue.

Front Genet

Shanghai Key Laboratory of Embryo Original Diseases, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Published: February 2021

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 , 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 activation process did not induce histological changes or abnormal DNA methylation occurrence.

Conclusion: MHY1485 for activation (IVA) is effective for ovarian rejuvenation and is a potential therapeutic treatment for POI patients.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890121PMC
http://dx.doi.org/10.3389/fgene.2020.603683DOI Listing

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