Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma

Neuropsychopharmacology. 2016 Oct;41(11):2749-58. doi: 10.1038/npp.2016.87. Epub 2016 Jun 9.


Adverse experiences in early life are risk factors for the development of behavioral and physiological symptoms that can lead to psychiatric and cognitive disorders later in life. Some of these symptoms can be transmitted to the offspring, in some cases by non-genomic mechanisms involving germ cells. Using a mouse model of unpredictable maternal separation and maternal stress, we show that postnatal trauma alters coping behaviors in adverse conditions in exposed males when adult and in their adult male progeny. The behavioral changes are accompanied by increased glucocorticoid receptor (GR) expression and decreased DNA methylation of the GR promoter in the hippocampus. DNA methylation is also decreased in sperm cells of exposed males when adult. Transgenerational transmission of behavioral symptoms is prevented by paternal environmental enrichment, an effect associated with the reversal of alterations in GR gene expression and DNA methylation in the hippocampus of the male offspring. These findings highlight the influence of both negative and positive environmental factors on behavior across generations and the plasticity of the epigenome across life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Psychological / physiology
  • Animals
  • Animals, Newborn
  • Avoidance Learning / physiology
  • DNA Methylation / physiology
  • Dark Adaptation
  • Disease Models, Animal
  • Environment*
  • Female
  • Gene Expression Regulation
  • Hippocampus / metabolism
  • Male
  • Maternal Deprivation*
  • Mice
  • Mice, Inbred C57BL
  • Pregnancy
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism*
  • Stress Disorders, Traumatic / etiology*
  • Stress Disorders, Traumatic / pathology
  • Stress Disorders, Traumatic / prevention & control*
  • Water Deprivation


  • Receptors, Glucocorticoid