Behavioural traits propagate across generations via segregated iterative-somatic and gametic epigenetic mechanisms

Nat Commun. 2016 May 13:7:11492. doi: 10.1038/ncomms11492.

Abstract

Parental behavioural traits can be transmitted by non-genetic mechanisms to the offspring. Although trait transmission via sperm has been extensively researched, epidemiological studies indicate the exclusive/prominent maternal transmission of many non-genetic traits. Since maternal conditions impact the offspring during gametogenesis and through fetal/early-postnatal life, the resultant phenotype is likely the aggregate of consecutive germline and somatic effects; a concept that has not been previously studied. Here, we dissected a complex maternally transmitted phenotype, reminiscent of comorbid generalized anxiety/depression, to elementary behaviours/domains and their transmission mechanisms in mice. We show that four anxiety/stress-reactive traits are transmitted via independent iterative-somatic and gametic epigenetic mechanisms across multiple generations. Somatic/gametic transmission alters DNA methylation at enhancers within synaptic genes whose functions can be linked to the behavioural traits. Traits have generation-dependent penetrance and sex specificity resulting in pleiotropy. A transmission-pathway-based concept can refine current inheritance models of psychiatric diseases and facilitate the development of better animal models and new therapeutic approaches.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Anxiety / genetics
  • Anxiety / psychology
  • Behavior, Animal / physiology*
  • DNA Methylation / genetics
  • Disease Models, Animal
  • Epigenesis, Genetic*
  • Female
  • Gametogenesis / physiology
  • Genomic Imprinting / physiology
  • Germ Cells / physiology*
  • Hypothermia / chemically induced
  • Hypothermia / genetics
  • Hypothermia / psychology
  • Male
  • Maternal Inheritance / physiology*
  • Metabolomics / methods
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Penetrance
  • Phenotype
  • Receptor, Serotonin, 5-HT1A / genetics
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Serotonin Receptor Agonists / pharmacology
  • Stress, Psychological / genetics
  • Stress, Psychological / psychology

Substances

  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • 8-Hydroxy-2-(di-n-propylamino)tetralin