Prenatal Adversity Alters the Epigenetic Profile of the Prefrontal Cortex: Sexually Dimorphic Effects of Prenatal Alcohol Exposure and Food-related Stress

Prenatal adversity or stress can have long-term consequences on developmental trajec-tories and health outcomes. Although the biological mechanisms underlying these effects are poorly understood, epigenetic modifications, such as DNA methylation, have the potential to link early-life environments to alterations in physiological systems, with long-term functional impli-cations. We investigated the consequences of two prenatal insults, prenatal alcohol exposure (PAE) and food-related stress, on DNA methylation profiles of the rat brain during early devel-opment. As these insults can have sex-specific effects on biological outcomes, we analyzed epige-nome-wide DNA methylation patterns in prefrontal cortex, a key brain region involved in cogni-tion, executive function, and behavior, of both males and females. We found sex-dependent and sex-concordant influences of these insults on epigenetic patterns. These alterations occurred in genes and pathways related to brain development and immune function, suggesting that PAE and food-related stress may reprogram neurobiological/physiological systems partly through central epigenetic changes, and may do so in a sex-dependent manner. Such epigenetic changes may re-flect the sex-specific effects of prenatal insults on long-term functional and health outcomes and may have important implications for understanding possible mechanisms underlying fetal alco-hol spectrum disorder and other neurodevelopmental disorders. Overall design: DNA methylation data from meDIP-seq of 30 rat samples, spanning three prenatal treatment groups (control, pair-fed, prenatal alcohol exposed) and both sexes. Prefrontal cortex samples were collected on postnatal day 22 (PN22). Each group/sex had n= 5. One sequencing run was performed for each sample (30 aligned bam files) and DNA methylation peaks were called using MACS2 following DNA processing (xls files).