Germ Cell Origins of Posttraumatic Stress Disorder Risk: The Transgenerational Impact of Parental Stress Experience
Open accessAbstract
Altered stress reactivity is a predominant feature of posttraumatic stress disorder (PTSD) and may reflect disease vulnerability, increasing the probability that an individual will develop PTSD following trauma exposure. Environmental factors, particularly prior stress history, contribute to the developmental programming of the hypothalamic-pituitary-adrenal stress axis. Critically, the consequences of stress experiences are transgenerational, with parental stress exposure impacting stress reactivity and PTSD risk in subsequent generations. Potential molecular mechanisms underlying this transmission have been explored in rodent models that specifically examine the paternal lineage, identifying epigenetic signatures in male germ cells as possible substrates of transgenerational programming. Here, we review the role of these germ cell epigenetic marks, including posttranslational histone modifications, DNA methylation, and populations of small noncoding RNAs, in the development of offspring stress axis sensitivity and disease risk.
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Offspring effects may be mediated, in part, by epigenetic changes in parental germ cells resulting from acquired parental stress exposures throughout life.
“Offspring effects may be mediated, in part, by epigenetic changes in parental germ cells resulting from acquired parental stress exposures throughout life 3,[168][169][170]”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [170]
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Fischer, L. W., Simas, J. N., Nunes, M., Mendes, T. B., Paccola, C. C., de Oliva, S. U., & Miraglia, S. M. (2026) · Andrology · doi:10.1111/andr.70418
- Authors
- Rodgers, A. B., & Bale, T. L.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Bale, Tracy L.
- ORCID
- Bale, Tracy L.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 78
- Issue
- 5
- Pages
- 307-314
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4526334
- OpenAlex
- W2170250876
- Cited by
- 91
- References
- 118
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 10 · 2021: 8 · 2020: 11 · 2019: 4 · 2018: 13 · 2017: 9 · 2016: 8 · 2015: 6
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (MH073030, MH091258, MH087597, MH099910, MH104184)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- post-traumatic stress disorder, transgenerational epigenetic inheritance, germ cells, hypothalamic-pituitary-adrenal axis, stress reactivity, developmental programming, histone modifications, DNA methylation, small RNA, paternal lineages
- MeSH terms
- Animals, Disease Models, Animal, Female, Germ Cells, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Pregnancy, Prenatal Exposure Delayed Effects, Stress Disorders, Post-Traumatic, Epigenomics
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