Transgenerational epigenetic inheritance: myths and mechanisms
Open accessAbstract
Since the human genome was sequenced, the term "epigenetics" is increasingly being associated with the hope that we are more than just the sum of our genes. Might what we eat, the air we breathe, or even the emotions we feel influence not only our genes but those of descendants? The environment can certainly influence gene expression and can lead to disease, but transgenerational consequences are another matter. Although the inheritance of epigenetic characters can certainly occur-particularly in plants-how much is due to the environment and the extent to which it happens in humans remain unclear.
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Increasing evidence indicates that epigenetic information can be inherited transgenerationally across a range of species, including humans, with effects manifesting in the F2 generation not subject to the original exposure.
“Increasing evidence indicates that epigenetic information can also be inherited transgenerationally across a range of species, including humans, with effects manifesting in the F2 generation (i.e., in grandchildren) not subject to the original exposure.”
From Ignoring the planet: A critical blind spot for research on ageing (2025) · cites this paper as [31]
The Conclusions (page unavailable) say transgenerational epigenetic inheritance is well documented in plants and some animals, but that there is little support for it in humans. The Implications for human health section (page unavailable) says most relevant studies concern intergenerational parental or grandparental exposure, rather than truly transgenerational inheritance. This contradicts the claim’s inclusion of humans and its characterization of the grandchildren as unexposed. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredEpigenetic mechanisms support biological adaptability to environmental perturbations and can pass these adaptive responses to future generations.
“Epigenetic mechanisms support biological adaptability to environmental perturbations and can pass these adaptive responses to future generations. This is in keeping with epigenetic intergenerational responses (IGRs) and transgenerational responses (TGRs) observed in humans and other mammals [31, 32].”
From Ignoring the planet: A critical blind spot for research on ageing (2025) · cites this paper as [31]
In “Epigenetic variation and the adaptive inheritance of acquired traits” (page not provided), the paper says epigenetic variation can respond to environmental cues and gives examples of effects inherited across generations. But it says whether these effects improve adaptive fitness is unclear and that concrete evidence for adaptive epigenetic inheritance is lacking. The Introduction and Conclusions (pages not provided) also caution that transgenerational epigenetic inheritance has little support in mammals, including humans. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe factors studied include endocrine disruptors, high fat diet, obesity, diabetes, undernourishment as well as trauma.
“The factors include endocrine disruptors, high fat diet, obesity, diabetes, undernourishment as well as trauma.”
From A critical view on transgenerational epigenetic inheritance in humans (2018) · cites this paper as [5]
In “Implications for human health” (page unavailable), the paper discusses high-fat diet and undernourishment as exposures studied for possible inherited effects; it also reports obesity in offspring as an outcome. “Epigenetic variation and the adaptive inheritance of acquired traits” discusses exposure to the fungicide vinclozolin. The cited passages do not establish obesity or diabetes as studied factors, or identify trauma as one; searches for those terms and endocrine disruptors did not substantiate the full list. (LLM, conf=0.86)
Experimental — accuracy not yet measuredHow much these changes are due to these factors, and to what extent, remains unclear.
“However, how much these changes are due to these factors, and to what extent, remains, unclear (261).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [261]
Numerous reports on transgenerational responses to environmental or metabolic factors in mice and rats have been published in the past 10 years.
“In the past 10 years, numerous reports on transgenerational responses to environmental or metabolic factors in mice and rats have been published (for a comprehensive review, see refs. 4–7).”
From A critical view on transgenerational epigenetic inheritance in humans (2018) · cites this paper as [5]
There is abundant evidence for intergenerational inheritance in plants and some animals.
“There is abundant evidence for intergenerational inheritance in plants and some animals 86,[95][96][97][98][99][100] , suggesting that this phenomenon might be involved in establishing early developmental patterning.”
From Advances in epigenetics link genetics to the environment and disease (2019) · cites this paper as [95]
Intergenerational inheritance might be involved in establishing early developmental patterning.
“There is abundant evidence for intergenerational inheritance in plants and some animals 86,[95][96][97][98][99][100] , suggesting that this phenomenon might be involved in establishing early developmental patterning.”
From Advances in epigenetics link genetics to the environment and disease (2019) · cites this paper as [95]
In plants, transgenerational epigenetic inheritance is well described and plant epialleles can be stable over many generations.
“In plants, TEI has also been well-described.Plant epialleles can be stable over many generations, and TEI is generally conveyed by RNA-directed DNA methylation (Fig. 3a)”
From Advances in epigenetics link genetics to the environment and disease (2019) · cites this paper as [95]
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Anwer, H., Morris, M. J., Noble, D. W. A., Nakagawa, S., & Lagisz, M. (2022) · Obesity Reviews · doi:10.1111/obr.13342 · Cited by 14 · see citing works
Epigenetic memories and the evolution of infectious diseases
McLeod, D. V., Wild, G., & Úbeda, F. (2021) · Nature Communications · doi:10.1038/s41467-021-24580-0 · Cited by 12 · see citing works
Ignoring the planet: A critical blind spot for research on ageing
Shiels, P., Neytchev, O., Borland, G., Germushkina, P., Johnson, R., Stenvinkel, P., & Woods, T. (2025) · Journal of Internal Medicine · doi:10.1111/joim.70032 · Cited by 4 · see citing works
- Authors
- Heard, E., & Martienssen, R. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Martienssen, Robert A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 157
- Issue
- 1
- Pages
- 95-109
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4020004
- OpenAlex
- W2040553259
- Cited by
- 1,864
- References
- 140
- Citations by year
- 2026: 107 · 2025: 114 · 2024: 118 · 2023: 177 · 2022: 169 · 2021: 157 · 2020: 178 · 2019: 201 · 2018: 172 · 2017: 171 · 2016: 117 · 2015: 139 · 2014: 41
- FWCI
- 14.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- Funders
- National Science Foundation
- Howard Hughes Medical Institute
- Gordon and Betty Moore Foundation
- Agence Nationale de la Recherche (ANR-10-IDEX-0001)
- National Institute of General Medical Sciences (GM067014, R01GM067014, R01GM076396)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- transgenerational epigenetic inheritance, epigenetics, environmental influences on gene expression, gene-environment interaction, epigenetic mechanisms
- MeSH terms
- Animals, Gene Expression Regulation, Germ Cells, Humans, Plants, DNA Methylation, Epigenesis, Genetic, Gene-Environment Interaction
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