Reprogramming of glucose metabolism of cumulus cells and oocytes and its therapeutic significance.

The aim of this review is to summarize our current understanding of the molecular mechanism for the glucose metabolism, especially pyruvate dehydrogenase (PDH), during oocyte maturation, as well as future perspectives of therapeutic strategies for aging focusing on metabolic regulation between aerobic glycolysis and the tricarboxylic acid (TCA) cycle/oxidative phosphorylation (OXPHOS). Each keyword alone or in combination was used to search from PubMed. Glucose metabolism is a dynamic process involving "On" and "Off" switches by the pyruvate dehydrogenase kinase (PDK)-PDH axis, which is crucial for energy metabolism and mitochondrial efficiency in cumulus cell differentiation and oocyte maturation. Activation of PDK suppresses the conversion of pyruvate to acetyl-coenzyme A (acetyl-CoA) through the inactivation of PDH, which allows the cumulus cells to supply sufficient amounts of pyruvate, lactate, and nicotinamide adenine dinucleotide phosphate (NADPH) to the oocytes. On the other hand, inactivation of PDK in oocytes can produce adenosine triphosphate (ATP) through a metabolic shift from aerobic glycolysis to the TCA cycle/OXPHOS. The metabolic balance between aerobic glycolysis and TCA cycle/OXPHOS presents us with a number of enzymes, ligands, receptors, and antioxidants that are potential therapeutic targets, some of which have already been successfully pursued to improve fertility outcomes. However, there are also many reports that question their efficacy. In conclusion, understanding the molecular mechanisms involved in the PDK-PDH axis is a crucial step to advance in novel therapeutic strategies to improve oocyte quality.