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 placental gene expression?DesignBlastocysts cultured with or without 2 mmol/L βOHB alone (‘βOHB’) combined 0.8 AcAc (‘Keto’) underwent embryo transfer. Transcriptional profiles sexed E14.5 placentae, liver, brain were examined via RNA-Sequencing DAVID functional analysis.Results: A sexually dimorphic response was observed. Keto both downregulated genes related oxidative phosphorylation specifically female liver. steroid biosynthetic processes, while treatment upregulated relevant blood vessel formation cell migration male placentae. Brain transcriptomes minimally affected. X-linked chromatin modifiers identified as differentially expressed, alluding a sex-specific regulatory mechanism.Conclusions: Transient perturbs liver expression demonstrating developmental programming effect that warrants future investigation offspring postnatal metabolic health.