Alcohol effects on the epigenome in the germline: Role in the inheritance of alcohol-related pathology

Alcohol. 2017 May:60:53-66. doi: 10.1016/j.alcohol.2016.12.007. Epub 2017 Mar 6.

Abstract

Excessive alcohol exposure has severe health consequences, and clinical and animal studies have demonstrated that disruptions in the epigenome of somatic cells, such as those in brain, are an important factor in the development of alcohol-related pathologies, such as alcohol-use disorders (AUDs) and fetal alcohol spectrum disorders (FASDs). It is also well known that alcohol-related health problems are passed down across generations in human populations, but the complete mechanisms for this phenomenon are currently unknown. Recent studies in animal models have suggested that epigenetic factors are also responsible for the transmission of alcohol-related pathologies across generations. Alcohol exposure has been shown to induce changes in the epigenome of sperm of exposed male animals, and these epimutations are inherited in the offspring. This paper reviews evidence for multigenerational and transgenerational epigenetic inheritance of alcohol-related pathology through the germline. We also review the literature on the epigenetic effects of alcohol exposure on somatic cells in brain, and its contribution to AUDs and FASDs. We note gaps in knowledge in this field, such as the lack of clinical studies in human populations and the lack of data on epigenetic inheritance via the female germline, and we suggest future research directions.

Keywords: Birth outcome; DNA methylation; Fetal alcohol; Germline transmission; Offspring anxiety behavior; Offspring stress response; Preconception alcohol.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcohol Drinking / adverse effects
  • Alcohol Drinking / genetics*
  • Alcohol Drinking / metabolism
  • Alcohol Drinking / pathology
  • Alcoholism / genetics*
  • Alcoholism / metabolism
  • Alcoholism / pathology
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Chromatin Assembly and Disassembly / drug effects
  • DNA Methylation / drug effects
  • Disease Models, Animal
  • Epigenesis, Genetic / drug effects*
  • Ethanol / adverse effects*
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Heredity
  • Humans
  • Inheritance Patterns*
  • Male
  • Pedigree
  • Risk Factors
  • Spermatozoa / drug effects*
  • Spermatozoa / metabolism
  • Spermatozoa / pathology

Substances

  • Ethanol