Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma
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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.
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These epigenetic processes may have evolved in order to program the phenotype to effectively and rapidly adapt to new environmental demands.
“these epigenetic processes may have evolved in order to program the phenotype to effectively and rapidly adapt to new environmental demands (Fischer, 2014;Gapp et al., 2016;Yeshurun & Hannan, 2019).”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Gapp et al., 2016
The Discussion (page unavailable) links environmental exposure to changes in DNA methylation and describes improved coping with challenging conditions in offspring of trauma-exposed males. It does not say these epigenetic processes evolved to program phenotypes for rapid adaptation to new environmental demands. (LLM, conf=0.82)
Experimental — accuracy not yet measuredEarly maternal separation resulted in decreased nr3c1 DNA methylation in the hippocampus and sperm cells, as well as poor coping behavior.
“Early maternal separation resulted in decreased nr3c1 DNA methylation in the hippocampus and sperm cells, as well as poor coping behavior.”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [205]
The Effects of MSUS and EE on GR Expression and Promoter Methylation section reports decreased GR (nr3c1) methylation in the hippocampus of exposed males and their offspring, and in sperm of exposed males. But the intervention combined maternal separation with unpredictable maternal stress, and the Effects of MSUS on Coping Behaviors in Aversive Conditions section reports more active coping in offspring, not poor coping. (LLM, conf=0.90)
Experimental — accuracy not yet measuredEnvironmental enrichment following stress exposure in the F0 could reverse and prevent some of the effects.
“another study demonstrated that environmental enrichment following stress exposure in the F0 could reverse and prevent some of the effects 205”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [205]
The Reversibility of Altered Responses in Aversive Conditions section reports that environmental enrichment after early-life stress reversed some altered responses in male offspring. However, the paper says enrichment was given to F1 males, not the F0 generation; the MSUS Treatment and Breeding section identifies F0 as the parents of those males. Page numbers were not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredWhen environmental enrichment was applied at weaning until adulthood, the behavioral and methylation effects were no longer observed in the F0 or F1.
“When environmental enrichment was applied at weaning until adulthood, the behavioral and methylation effects were no longer observed in the F0 or F1.”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [205]
The Environmental Enrichment section says mice received enrichment from weaning to adulthood. The Reversibility of Altered Responses section reports normalized behavior in enriched F1 males and behavioral changes in their F2 offspring; the GR Expression and Promoter Methylation section reports correction of some methylation changes in F1 sperm and F2 offspring. The claim incorrectly names F0 rather than F2, and overstates the methylation result: an alteration at CpG4 remained in F2 offspring despite paternal enrichment. (LLM, conf=0.87)
Experimental — accuracy not yet measuredEarly postnatal exposure of male mice to traumatic stress resulted in offspring that were more capable of responding to adversity in adulthood, and these effects appeared to be epigenetically regulated.
“Early postnatal exposure of male mice to traumatic stress resulted in offspring that were more capable of responding to adversity in adulthood, and these effects appeared to be epigenetically regulated [82].”
If the father's exposure occurred when they reached adulthood rather than in early life, no effect on offspring behavior was observed.
“Interestingly, if the father’s exposure occurred when they reached adulthood rather than in early life, no effect on offspring behavior was observed.”
From Biological Embedding of Early-Life Adversity and a Scoping Review of the Evidence for Intergenerational Epigenetic Transmission of Stress and Trauma in Humans (2023) · cites this paper as [82]
The Discussion (page unavailable) reports that offspring behavior was normalized when fathers exposed to trauma in early life received environmental enrichment in adulthood. Our copy does not report a comparison in which fathers were first exposed to trauma in adulthood, so it cannot establish the claimed absence of an offspring effect. (LLM, conf=0.75)
Experimental — accuracy not yet measured
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- Authors
- Gapp, K., Bohacek, J., Grossmann, J., Brunner, A. M., Manuella, F., Nanni, P., & Mansuy, I. M.
- Affiliations
- University of Zurich (CH)
- Corresponding author
- Mansuy, Isabelle M
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2016-06-09
- Volume
- 41
- Issue
- 11
- Pages
- 2749-2758
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC5026744
- OpenAlex
- W2411112200
- Cited by
- 172
- References
- 43
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 15 · 2023: 19 · 2022: 24 · 2021: 16 · 2020: 22 · 2019: 10 · 2018: 29 · 2017: 13 · 2016: 3
- FWCI
- 9.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- environmental enrichment, transgenerational transmission, maternal separation, maternal stress, glucocorticoid receptor, DNA methylation, hippocampus, sperm epigenetics, epigenetic plasticity, coping styles, adverse childhood experiences
- MeSH terms
- Adaptation, Psychological, Animals, Animals, Newborn, Avoidance Learning, Dark Adaptation, Disease Models, Animal, Environment, Female, Gene Expression Regulation, Hippocampus, Male, Maternal Deprivation, Mice, Inbred C57BL, Pregnancy, Prenatal Exposure Delayed Effects, Receptors, Glucocorticoid, Water Deprivation, DNA Methylation, Stress Disorders, Traumatic, Mice
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