α-Ketoglutarate enhances bovine oocyte maturation and embryo development: insights from metabolomic and transcriptomic profiling.

Oocyte quality, governed by metabolic and epigenetic regulation, is essential for fertilization and embryogenesis. This study aimed to elucidate the dose-dependent and multifaceted roles of α-ketoglutarate (α-KG) in modulating the molecular and metabolic dynamics of cumulus-oocyte complexes (COCs) during in vitro maturation (IVM). Notably, supplementation with 100 μM α-KG resulted in the most pronounced improvement in maturation and developmental outcomes. α-KG remolds energy metabolism in both oocytes and their cumulus cells (CCs) during maturation via suppression of the citric cycle (TCA cycle) and pentose phosphate pathway (PPP), while enhancing glycolysis and β-oxidation in oocytes, alongside enhanced amino acids related to the methionine salvage pathway and folate cycle. Conversely, CCs exhibited a low metabolic status during maturation, characterized by suppressed glycolysis, the TCA cycle, β-oxidation, and fatty acid levels, suggesting a metabolic shift to prioritize oocyte support. These findings underscore a synergistic yet divergent metabolic adaptation: oocytes amplify energy and biosynthesis pathways, while CCs adopt a catabolic conservation strategy. Critically, α-KG's modulation of cyclic nucleotides (cAMP/cGMP) highlights its role in relieving meiotic arrest, linking metabolic shifts to cell cycle regulation. This study fills a crucial gap in our understanding, elucidating how α-KG regulates the environment around follicles and laying the groundwork for utilizing α-KG in reproductive technology to enhance embryo survival rates.