Paternal transgenerational epigenetic mechanisms mediating stress phenotypes of offspring

Ashley M. Cunningham, Deena M. Walker, Eric J. Nestler

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations


Depression and anxiety risk are highly influenced by both genetic and environmental factors. Recently, it has been proposed that epigenetic mechanisms may also contribute to the transmission of both depression- and anxiety-related behaviors across multiple generations. This review highlights long-lasting epigenetic alterations observed in offspring of fathers, including some distinct effects on male and female offspring, in animal models. Available evidence emphasizes how both the developmental time point and the type of paternal stress (social vs. asocial) influence the complex transmission patterns of these phenotypes to future generations. This research is critical in understanding the factors that influence risk for depression and anxiety disorders and has the potential to contribute to the development of innovative treatments that can more precisely target vulnerable populations.

Original languageEnglish (US)
Pages (from-to)271-280
Number of pages10
JournalEuropean Journal of Neuroscience
Issue number1
StatePublished - Jan 2021
Externally publishedYes


  • epigenetics
  • sperm
  • transgenerational stress

ASJC Scopus subject areas

  • Neuroscience(all)


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