Paternal Transmission of Stress-Induced Pathologies
Open accessAbstract
Background There has been recent interest in the possibility that epigenetic mechanisms might contribute to the transgenerational transmission of stress-induced vulnerability. Here, we focused on possible paternal transmission with the social defeat stress paradigm.Methods Adult male mice exposed to chronic social defeat stress or control nondefeated mice were bred with normal female mice, and their offspring were assessed behaviorally for depressive- and anxiety-like measures. Plasma levels of corticosterone and vascular endothelial growth factor were also assayed. To directly assess the role of epigenetic mechanisms, we used in vitro fertilization (IVF); behavioral assessments were conducted on offspring of mice from IVF-control and IVF-defeated fathers.Results We show that both male and female offspring from defeated fathers exhibit increased measures of several depression- and anxiety-like behaviors. The male offspring of defeated fathers also display increased baseline plasma levels of corticosterone and decreased levels of vascular endothelial growth factor. However, most of these behavioral changes were not observed when offspring were generated through IVF.Conclusions These results suggest that, although behavioral adaptations that occur after chronic social defeat stress can be transmitted from the father to his male and female F1 progeny, only very subtle changes might be transmitted epigenetically under the conditions tested.
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In the social defeat model, results were not observed when offspring were generated by in vitro fertilization, implicating behavioral, rather than germ cell epigenetic, influence.
“However, these results were not observed when offspring were generated by in vitro fertilization, implicating behavioral, rather than germ cell epigenetic, influence.”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [204]
The Results report that most behavioral differences seen after natural breeding were absent in IVF offspring, and the Discussion interprets this as suggesting that most transmission occurs through behavioral mechanisms. But the Results also report a small, significant IVF effect in the forced swim test, and the Discussion allows a limited epigenetic role. The claim overstates the finding by saying the results were not observed with IVF and contrasting behavioral with germ-cell epigenetic influence without that qualification. Page numbers were not supplied in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn a social defeat model of stress, male and female F1 mice exhibited altered behaviors, and male F1 had a broader range of affected behaviors.
“in a social defeat model of stress, male and female F1 mice exhibited altered behaviors, and male F1 had a broader range of affected behaviors 204”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [204]
Paternal transmission of stress sensitivity occurs.
“Recent work has indicated that there is paternal transmission of stress sensitivity (28).”
From Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress (2014) · cites this paper as [28]
Offspring of fathers that underwent RSDS display increased depression- and anxiety-related behavioral responses to stress.
“Offspring of fathers that underwent RSDS display increased depression- and anxiety-related behavioral responses to stress (28).”
From Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress (2014) · cites this paper as [28]
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- Authors
- Dietz, D. M., LaPlant, Q., Watts, E. L., Hodes, G. E., Russo, S. J., Feng, J., Oosting, R. S., Vialou, V., & Nestler, E. J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Utrecht University (NL)
- Corresponding author
- Nestler, Eric J.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 70
- Issue
- 5
- Pages
- 408-414
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3217197
- OpenAlex
- W2087713076
- Cited by
- 346
- References
- 29
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 14 · 2023: 21 · 2022: 15 · 2021: 23 · 2020: 12 · 2019: 29 · 2018: 37 · 2017: 26 · 2016: 25 · 2015: 28 · 2014: 38 · 2013: 30 · 2012: 24
- FWCI
- 11.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P50 MH66172)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- transgenerational epigenetic inheritance, paternal transmission, social defeat stress, depression-like behavior, anxiety-like behavior, corticosterone, vascular endothelial growth factor, in vitro fertilization, offspring behavior
- MeSH terms
- Animals, Anxiety, Corticosterone, Depression, Disease Models, Animal, Father-Child Relations, Fathers, Female, Fertilization in Vitro, Humans, Male, Mice, Inbred C57BL, Social Behavior, Stress, Psychological, Vascular Endothelial Growth Factor A, Mice
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