Intergenerational Effects of Alcohol: A Review of Paternal Preconception Ethanol Exposure Studies and Epigenetic Mechanisms in the Male Germline

Abstract

While alcohol use disorder (AUD) is a highly heritable psychiatric disease, efforts to elucidate that heritability by examining genetic variation (e.g., single nucleotide polymorphisms) have been insufficient to fully account for familial AUD risk. Perhaps not coincidently, there has been a burgeoning interest in novel non-genomic mechanisms of inheritance (i.e., epigenetics) that are shaped in the male or female germ cells by significant lifetime experiences such as exposure to chronic stress, malnutrition, or drugs of abuse. While many epidemiological and preclinical studies have long pointed to a role for the parental preconception environment in offspring behavior, over the last decade many studies have implicated a causal relationship between the environmentally-sensitive sperm epigenome and intergenerational phenotypes. This critical review will detail the heritable effects of alcohol and the potential role for epigenetics.