Transgenerational Abnormalities Induced by Paternal Preconceptual Alcohol Drinking: Findings from Humans and Animal Models

Curr Neuropharmacol. 2022;20(6):1158-1173. doi: 10.2174/1570159X19666211101111430.


Alcohol consumption during pregnancy and lactation is a widespread preventable cause of neurodevelopmental impairment in newborns. While the harmful effects of gestational alcohol use have been well documented, only recently, the role of paternal preconceptual alcohol consumption (PPAC) prior to copulating has drawn specific epigenetic considerations. Data from human and animal models have demonstrated that PPAC may affect sperm function, eliciting oxidative stress. In newborns, PPAC may induce changes in behavior, cognitive functions, and emotional responses. Furthermore, PPAC may elicit neurobiological disruptions, visuospatial impairments, hyperactivity disorders, motor skill disruptions, hearing loss, endocrine, and immune alterations, reduced physical growth, placental disruptions, and metabolic alterations. Neurobiological studies on PPAC have also disclosed changes in brain function and structure by disrupting the growth factors pathways. In particular, as shown in animal model studies, PPAC alters brain nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF) synthesis and release. This review shows that the crucial topic of lifelong disabilities induced by PPAC and/or gestational alcohol drinking is quite challenging at the individual, societal, and familial levels. Since a nontoxic drinking behavior before pregnancy (for both men and women), during pregnancy, and lactation cannot be established, the only suggestion for couples planning pregnancies is to completely avoid the consumption of alcoholic beverages.

Keywords: Neurotrophins; brain; epigenetics; fetal alcohol spectrum disorders; fetal alcohol syndrome; paternal preconceptual alcohol consumption; transgenerational changes.

Publication types

  • Review

MeSH terms

  • Alcohol Drinking
  • Animals
  • Disease Models, Animal
  • Ethanol / pharmacology
  • Female
  • Fetal Alcohol Spectrum Disorders* / etiology
  • Fetal Alcohol Spectrum Disorders* / metabolism
  • Humans
  • Infant, Newborn
  • Placenta / metabolism
  • Pregnancy


  • Ethanol