Cited by 116Birth, Development, and HealthEpigenetics and DNA MethylationStress Responses and Cortisol

Transgenerational inheritance of behavioral and metabolic effects of paternal exposure to traumatic stress in early postnatal life: evidence in the 4th generation

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van Steenwyk, Gretchen, Roszkowski, Martin, Manuella, Francesca, Franklin, Tamara B, Mansuy, Isabelle M·2018·Environmental Epigenetics

Abstract

In the past decades, evidence supporting the transmission of acquired traits across generations has reshaped the field of genetics and the understanding of disease susceptibility. In humans, pioneer studies showed that exposure to famine, endocrine disruptors or trauma can affect descendants, and has led to a paradigm shift in thinking about heredity. Studies in humans have however been limited by the low number of successive generations, the different conditions that can be examined, and the lack of mechanistic insight they can provide. Animal models have been instrumental to circumvent these limitations and allowed studies on the mechanisms of inheritance of environmentally induced traits across generations in controlled and reproducible settings. However, most models available today are only intergenerational and do not demonstrate transmission beyond the direct offspring of exposed individuals. Here, we report transgenerational transmission of behavioral and metabolic phenotypes up to the 4th generation in a mouse model of paternal postnatal trauma (MSUS). Based on large animal numbers (up to 124 per group) from several independent breedings conducted 10 years apart by different experimenters, we show that depressive-like behaviors are transmitted to the offspring until the third generation, and risk-taking and glucose dysregulation until the fourth generation via males. The symptoms are consistent and reproducible, and persist with similar severity across generations. These results provide strong evidence that adverse conditions in early postnatal life can have transgenerational effects, and highlight the validity of MSUS as a solid model of transgenerational epigenetic inheritance.

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  1. [23]Skinner MK, Manikkam M, Tracey R, Nilsson E, Haque MM, Guerrero-Bosagna C. Ancestral DDT exposures promote epigenetic transgenerational inheritance of obesity. BMC Med 2013; 11: 228. 24228800 PMC3853586

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Authors
van Steenwyk, G., Roszkowski, M., Manuella, F., Franklin, T. B., & Mansuy, I. M.
Affiliations
  • Laboratory of Neuroepigenetics, Brain Research Institute, Faculty of Medicine, University of Zurich & Institute for Neuroscience, Department of Health Science and Technology, ETH Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
  • University of Zurich (CH)
  • Dalhousie University (CA)
Corresponding author
Mansuy, Isabelle M
Venue
Environmental Epigenetics
Published
2018-04-01
Volume
4
Issue
2
Pages
dvy023-dvy023
ISSN
  • 1674-5507 (ISSN-L)
  • 2058-5888
OpenAlex
W2897521748
Cited by
116
References
62
Citations by year
2026: 9 · 2025: 11 · 2024: 14 · 2023: 20 · 2022: 12 · 2021: 12 · 2020: 17 · 2019: 19 · 2017: 1
FWCI
13.25
Type
journal article
Language
en
Open access
Locations
  • Current Zoology (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by-nc)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc)
  • ETH Zürich Research Collection
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • National Science Foundation
  • Novartis Foundation
  • Branco Weiss Fellowship – Society in Science
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
  • Fondation pour la Recherche Médicale
  • Novartis Stiftung für Medizinisch-Biologische Forschung
  • Universität Zürich
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
transgenerational epigenetic inheritance, postpartum stress, depression-like behavior, risk-taking, glucose dysregulation, metabolic phenotypes, behavioral phenotypes, intergenerational transmission

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