Enhanced glycolysis in granulosa cells promotes the activation of primordial follicles through mTOR signaling

• DOI: 10.1038/s41419-022-04541-1
• Publication Date: 2022-01-27T07:02:38Z
• Authors: Xiaodan Zhang; Wenbo Zhang; Zhijuan Wang; Nana Zheng; Feifei Yuan; Biao Li; Xuelan Li; Ling Deng; Min Lin; Xin Chen; Meijia Zhang
• Keywords: PKM2

Abstract In mammals, nonrenewable primordial follicles are activated in an orderly manner to maintain the longevity of reproductive life. Mammalian target rapamycin (mTOR)-KIT ligand (KITL) signaling pre-granulosa cells and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-forkhead Box O3a (FOXO3a) oocytes important for follicle activation. The activation process is accompanied by enhancement energy metabolism, but causal relationship unclear. present study, levels glycolysis-related proteins GLUT4, HK1, PFKL, PKM2 were significantly increased granulosa decreased during mouse primordial-to-primary transition. Both short-term pyruvate deprivation vitro acute fasting vivo gene protein levels, AMPK activity, mTOR activity ovaries. downstream pathways Akt FOXO3a phosphorylated, resulting blockade glycolysis 2-deoxyglucose (2-DG), not communication network between oocyte KIT inhibitor ISCK03, deprivation-promoted activity. Glycolysis was also human transition, promoted increasing ovarian tissues. Taken together, enhanced promotes through signaling. These findings provide new insight into glycolytic disorders POI/PCOS.