No abstract

Prenatal alcohol exposure (PAE) is associated with changes to offspring DNA methylation and adverse neurodevelopmental outcomes. Prior studies have utilised candidate gene or microarray approaches resulting in biased representation of the methylome. We employed an established experimental murine model of moderate PAE until gestational days 8-10, with genome-wide DNA methylation sequencing of neonatal brain and liver. Although global DNA methylation levels were generally preserved, we detected 78 alcohol-sensitive regions in neonatal brain, and 759 alcohol-sensitive regions in neonatal liver (p < 0.05 and delta beta > 0.05). Affected coding regions were significantly enriched in genes involved in neurodevelopmental pathways, but behavioural outcomes were unaltered in adult littermates. Seven alcohol-sensitive regions identified in mice were statistically replicated in a human cohort of adolescents with fetal alcohol spectrum disorder (FASD) and known to be linked with traits related to facial morphology, intelligence, educational attainment, autism, schizophrenia, ageing and haematological disorders in the GWAS catalogue. The high methyl donor diet (HMD) across pregnancy partially protected against the effects of alcohol on DNA methylation in offspring tissues. Collectively this study provides a comprehensive evaluation of PAE on offspring DNA methylation and suggests prenatal dietary intervention may be a warranted mitigation strategy.