The central role of pyruvate metabolism on the epigenetic and molecular maturation of bovine cumulus-oocytes complexes.

Pyruvate, the end-product of glycolysis in aerobic conditions, is produced by cumulus cells, and is converted in Acetyl-CoA into the mitochondria of both cumulus cells (CCs) and oocytes as a master fuel input for the tricarboxylic acid cycle (TCA). The citrate generated in the TCA cycle can be directed to the cytoplasm and converted back to acetyl-CoA, being driven to lipid synthesis or, still, being used as the substrate for histones acetylation. This work aimed to verify the impact of pyruvate metabolism on the dynamic of lysine 9 histone 3 acetylation (H3K9ac) and RNA transcription in bovine cumulus-oocyte complexes during in vitro maturation (IVM). Bovine oocytes were IVM for 24h in three experimental groups: Control [IVM medium], sodium dichloroacetate [DCA, a stimulator of pyruvate oxidation in acetyl-CoA] or sodium iodoacetate [IA, a glycolysis inhibitor]. Our results show that both treatments change the metabolic profile of oocytes and CCs, stimulating the use of lipids for energy metabolism in the gamete. This leads to changes in the dynamics of H3K9ac during the IVM in both oocytes and CCs with impact on the synthesis of new transcripts in CCs. A total of 148 and 356 differentially expressed genes were identified in DCA and IA oocytes groups, respectively, when compared to the control group. In conclusion, disorders in pyruvate metabolism during maturation stimulate the beta-oxidation pathway, altering the mitochondrial metabolism, with consequences for the mRNA content of bovine oocytes.