O-059 ntermetabolites of cholesterol synthesis in granulosa cell and oocyte aging

Abstract With the development of society, there has been a significant delay in female fertility and an increasing desire for childbearing among females advanced maternal age recent decades. Nevertheless, women over 35 years old have more risk infertility miscarriage compared to young women, due decreased oocyte quality. These changes are mainly caused by meiotic defects, especially aneuploidy. Therefore, exploring mechanisms aging-related defects aneuploidy oocytes is great improving pregnancy outcomes aged women. Oocytes enveloped granulosa cells (GCs) form follicles, which constitute reproductive units ovaries. GCs metabolic community with growth maturation. Numerous studies reported that coupling between could affect process meiosis resumption, spindle assembly, chromatin arrangement. Maternal aging related disruption oocyte-GC interactions leads disorders process. abnormal important reason quality oocytes. To further clarify during ovarian aging, we systematically characterized dynamic overall transcriptomic landscapes from mice throughout (during growing [GO], full-grown [FGO], metaphase I [MI] [MIO], II [MII] [MIIO] phases). Data revealed mevalonate (MVA) pathway, essential pathway uses acetyl-CoA produce cholesterol isoprenoids, was specifically highly expressed resumption meiosis, expression MVA age. Atorvastatin-mediated inhibition metabolism first polar body extrusion (PBE) rate, increased cumulus-oocyte complexes (COCs). Further showed effect on regulated protein isoprenoylation mediated inter-metabolites synthesis. Importantly, upregulation ameliorate depletion reserve, decrease improve In conclusion, metabolite cell factor determining quality; critical regulator maturation euploidy oocytes, age-associated abnormalities contribute aneuploidy; Supplementation synthesis new therapeutic target clinical intervention Trial registration number XXXX