(088) The Essential Role of O-GlcNAcylation in the Testis Aging

Abstract Introduction With the delay of reproductive age, disorders related to advanced age have gradually attracted widespread attention. Studies shown that decline in male fertility due aging is manifested as a decrease semen parameters and spermatogenetic cells histologically. O-GlcNAc (O-acetylglucosamine) glycosylation post-translational modification exists widely cells. The level UDP-GlcNAc, which substrate O-GlcNAcylation, changes rapidly with various nutrients external factors. Therefore, O-GlcNAcylation can respond glucose, amino acid, fatty nucleoside metabolism, considered be an important sensor cellular metabolism. previous study our project found aged testis tissue was significantly increased, so this aimed explore specific mechanism involved testicular aging. Objective 1.Explore pattern 2.Mimic high state mice young mice, effect elevated on testis. 3.Reveal role key proteins modified by Methods Mice were injected intraperitoneally OGA inhibitor Thiamet-G for 35 days increase simulate CASA system used detect parameters, chromosome spreading technology mouse meiosis. Using protein profiling technology, differentially screened, point mutations made at their sites Results increased. After injecting into days, High damaged sperm parameter, decreased thickness seminiferous epithelium increased apoptosis Chromosome experiments showed that, γH2Ax, marker DNA double strand breaks, stained unusually autosomes pachytene spermatocytes. elevation γH2Ax affected transition spermatocytes diplotene. Importantly, we Hyou1 mice. promotes degradation Hyou1. An site identified S634 mutation stability exerts protective roles Conclusions In leads arrest spermatocyte meiosis affecting damage repair pathway. roles. This revealed first time aging, provided new therapeutic target clinically delaying treating infertility. Disclosure No