Acetoacetate and β-hydroxybutyrate reduce mouse embryo viability via differential metabolic and epigenetic mechanisms

Abstract

Research question: Does the ketone acetoacetate (AcAc) alone, or combined with β-hydroxybutyrate (βOHB), impact mouse embryo development, metabolism, histone acetylation and viability? Design: Pronucleate mouse oocytes were cultured in vitro in G1/G2 media supplemented with ketones (AcAc or AcAc + βOHB) at concentrations representing those in maternal serum during pregnancy (0.04 mmol/l AcAc, 0.1 mmol/l βOHB), standard diet consumption (0.1 mmol/l AcAc, 0.25 mmol/l βOHB), ketogenic diet consumption (0.8 mmol/l AcAc, 2 mmol/l βOHB) and diabetic ketoacidosis (2 mmol/l AcAc, 4 mmol/l βOHB). Day 5 blastocysts were assessed for cell allocation, glucose metabolism and histone acetylation. Day 4 bl..