Pyruvate metabolism alters the epigenetic and transcriptional profile of bovine oocytes.
Pyruvate, the end-product of glycolysis in aerobic conditions, is converted into acetyl-CoA inside the mitochondria of oocytes as a master fuel input for the tricarboxylic acid (TCA) cycle. 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, alternatively, being used as the substrate for histones acetylation. This work aimed to verify the impact of pyruvate metabolism on the dynamics of lysine 9 histone 3 acetylation (H3K9ac) and RNA transcription in bovine oocytes during in vitro maturation (IVM). Bovine cumulus-oocyte complexes were subjected to IVM for 24 h considering three experimental groups: Control [IVM medium], sodium dichloroacetate [DCA, a stimulator of pyruvate oxidation into acetyl-CoA] or sodium iodoacetate [IA, a glycolysis inhibitor]. Our results show that both treatments change the metabolic profile of oocytes, stimulating the use of lipids for energy metabolism in the gamete. This leads to changes during IVM in the dynamics of H3K9ac, consequently impacting the oocyte transcriptional profile. A total of 148 and 356 differentially expressed genes were identified in DCA and IA oocyte groups, respectively, when compared to the control group. In summary, our results indicate that changes in the pyruvate metabolism induce the activation of metabolic pathways, such as lipid metabolism, and these metabolic alterations alter acetyl-CoA availability and H3K9ac levels at 24 h of IVM, consequently impacting the mRNA content of bovine oocytes. Overall design: Bovine Oocytes were submitted to IVM in a maturation medium supplemented with dichloroacetate (DCA) or iodoacetate (IA) for 24h.