Glucose activates the primordial follicle through the AMPK/mTOR signaling pathway

Abstract

Background: We have previously found that the energy level in sows affects the activation of primordial follicles. Glucose is the primary metabolic substrate of dietary energy and its effect and mechanism of action with regards to the activation and development of primordial follicle remain unclear. Studies utilizing several different animal cells have shown that energy stress, induced by glucose starvation, activates AMPK and participates in a variety of cellular processes by regulating the Hippo and mTOR signaling pathways. However, whether glucose can affect primordial follicle activation through the above pathways has not been reported. Methods: We developed an in vitro culture system for mouse ovaries to investigate the effects of glucose on the primordial follicle activation. Protein expression of AMPK-Hippo-YAP and AMPK-mTOR pathway was investigated under glucose starvation and optimal glucose level treatment. Then, ovaries were treated with AICAR or Compound C in vitro to explore the effect of AMPK activation or inhibition on primordial follicle activation, and the changes of AMPK-Hippo-YAP and AMPK-mTOR signaling pathways. Finally, investigated the signaling pathways affected by glucose potentially affecting the primordial follicle activation in vivo. Results: The glucose was an essential nutrient for primordial follicle activation and we identified 25 mM glucose as the optimal level (P < .05) for the primor-dial follicle activation in vitro. The glycolysis pathway was involved in primordial follicle activation (P