A maternal ketogenic diet alters oviduct fluid nutrients and embryo histone acetylation in mice.

In Brief: A ketogenic diet (KD) elevates blood β-hydroxybutyrate to concentrations that are known to perturb the development, metabolism, histone acetylation and viability of preimplantation mouse embryos in culture. This study shows that a maternal KD changes available nutrient levels in the oviduct, leading to altered embryo development and epigenetic state in vivo.

Abstract: A ketogenic diet elevates blood β-hydroxybutyrate to concentrations that perturb the development, metabolism, histone acetylation (H3K27ac) and viability of preimplantation mouse embryos in vitro.

Preimplantation embryo exposure to ketone bodies exerts sex-specific effects on mouse fetal and placental transcriptomes.

Research Question: Does in vitro exposure of preimplantation mouse embryos to the ketone bodies β-hydroxybutyrate (βOHB) and acetoacetate (AcAc) impact post-transfer fetal and placental gene expression?

Design: Blastocysts cultured in vitro with or without 2 mmol/l βOHB alone ('βOHB') or combined with 0.8 mmol/l AcAc ('Keto') underwent embryo transfer. Transcriptional profiles of sexed placenta, liver and brain at gestational day 14.

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

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.

β-hydroxybutyrate reduces blastocyst viability via trophectoderm-mediated metabolic aberrations in mice.

Study Question: What is the effect of the ketone β-hydroxybutyrate (βOHB) on preimplantation mouse embryo development, metabolism, epigenetics and post-transfer viability?

Summary Answer: In vitro βOHB exposure at ketogenic diet (KD)-relevant serum concentrations significantly impaired preimplantation mouse embryo development, induced aberrant glycolytic metabolism and reduced post-transfer fetal viability in a sex-specific manner.

What Is Known Already: A maternal KD in humans elevates gamete and offspring βOHB exposure during conception and gestation, and in rodents is associated with an increased time to pregnancy, and altered offspring organogenesis, post-natal growth and behaviour, suggesting a developmental programming effect. In vitro exposure to βOHB at supraphysiological concentrations (8-80 mM) perturbs preimplantation mouse embryo development.