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

Alexandre A Lussier,Michael S Kobor,Joanne Weinberg,Martin Hirst,Michelle Moksa,Tamara S Bodnar

doi:10.3390/genes12111773

Abstract

Prenatal adversity or stress can have long-term consequences on developmental trajectories 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 implications. 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 development. As these insults can have sex-specific effects on biological outcomes, we analyzed epigenome-wide DNA methylation patterns in prefrontal cortex, a key brain region involved in cognition, 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 reflect the sex-specific effects of prenatal insults on long-term functional and health outcomes and have important implications for understanding possible mechanisms underlying fetal alcohol spectrum disorder and other neurodevelopmental disorders.

Highlights

Neurodevelopmental and psychiatric disorders may be partly rooted in early-life environments, which can have profound influences on cognitive, neurobiological, and physiological outcomes
Given that prenatal alcohol exposure and pair-feeding may share some common pathways in the reprogramming of biological systems, we investigated Differentially Methylated Region (DMR) shared between these two prenatal exposures
We found no overlaps between PF-associated DMRs and autism spectrum disorder (ASD) genes identified at either the genetic or epigenetic level, suggesting potentially distinct pathways between neurodevelopmental disorders and physiological changes induced by food-related stress

Summary

Introduction

Neurodevelopmental and psychiatric disorders may be partly rooted in early-life environments, which can have profound influences on cognitive, neurobiological, and physiological outcomes. The mechanisms linking environmental exposures to neurodevelopmental outcomes are not fully understood, one prevailing hypothesis is that the effects of early-life challenges become biologically embedded through epigenetic mechanisms, such as histone modifications, non-coding RNA expression, and DNA methylation (DNAm) [5,6]. The latter is the most commonly studied epigenetic modification and involves the addition of a methyl residue to the cytosines. DNAm is relatively stable over time and may capture the effects of environmental exposures to modulate long-term gene expression, functional outcomes, and health [7]

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