Developmental toxicant exposures and sex-specific effects on epigenetic programming and cardiovascular health across generations
Open accessAbstract
Despite substantial strides in diagnosis and treatment, cardiovascular diseases (CVDs) continue to represent the leading cause of death in the USA and around the world, resulting in significant morbidity and loss of productive years of life. It is increasingly evident that environmental exposures during early development can influence CVD risk across the life course. CVDs exhibit marked sexual dimorphism, but how sex interacts with environmental exposures to affect cardiovascular health is a critical and understudied area of environmental health. Emerging evidence suggests that developmental exposures may have multi- and transgenerational effects on cardiovascular health, with potential sex differences; however, further research in this important area is urgently needed. Lead (Pb), phthalate plasticizers, and perfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants with numerous adverse human health effects. Notably, recent evidence suggests that developmental exposure to each of these toxicants has sex-specific effects on cardiovascular outcomes, but the underlying mechanisms, and their effects on future generations, require further investigation. This review article will highlight the role for the developmental environment in influencing cardiovascular health across generations, with a particular emphasis on sex differences and epigenetic mechanisms. In particular, we will focus on the current evidence for adverse multi and transgenerational effects of developmental exposures to Pb, phthalates, and PFAS and highlight areas where further research is needed.
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PFAS exposure causes epigenetic changes passed to future generations, with high risk for future generations.
“| Genetic Effects | Epigenetic changes passed to future generations. | High | Future Generations | Long-term generational effects | [236] |”
From Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS (2025) · cites this paper as [236]
The ‘Developmental PFAS exposure and cardiovascular health’ section reports PFAS-associated epigenetic changes, and Figure 2 describes possible effects on future generations. But the ‘Multi- and transgenerational effects’ section says epigenetic effects were not investigated in the studies reporting transgenerational PFAS outcomes, and that germline effects remain poorly understood. The paper therefore does not establish that PFAS-induced epigenetic changes are passed on or that future generations face a high risk. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPFAS exposure has potential generational impacts due to epigenetic changes.
“with potential generational impacts due to epigenetic changes”
From Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS (2025) · cites this paper as [236]
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Ma, S., Xu, C. Y., Ma, J., Wang, Z., Zhang, Y., Shu, Y., & Mo, X. (2019) · Environmental Pollution · doi:10.1016/j.envpol.2019.112971 · Cited by 47 · see citing works
Xu, X., Ni, H., Guo, Y., Lin, Y., Ji, J., Jin, C., Yuan, F., Feng, M., Ji, N., Zheng, Y., et al. (2021) · Environmental Pollution · doi:10.1016/j.envpol.2021.118112 · Cited by 46 · see citing works
The non‐genetic paternal factors for congenital heart defects: A systematic review and meta‐analysis
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Sanders, A. P., Svensson, K., Gennings, C., Burris, H. H., Oken, E., Amarasiriwardena, C. J., Basnet, P., Pizano-Zárate, M. L., Schnaas, L., Tamayo‐Ortiz, M., et al. (2018) · Environment International · doi:10.1016/j.envint.2018.08.038 · Cited by 44 · see citing works
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The Association Between Perfluoroalkyl Substances and Lipids in Cord Blood
Spratlen, M. J., Perera, F. P., Lederman, S. A., Robinson, M., Kannan, K., Herbstman, J. B., & Trasande, L. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz024 · Cited by 43 · see citing works
Low-level Chronic Lead Exposure Impairs Neural Control of Blood Pressure and Heart Rate in Rats
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Phthalate exposure linked to high blood pressure in Chinese children
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Brehm, E., Zhou, C., Gao, L., & Flaws, J. A. (2020) · Reproductive Toxicology · doi:10.1016/j.reprotox.2020.10.009 · Cited by 41 · see citing works
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Flagged first, then by citations
4 of the 264 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
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A precision environmental health approach to prevention of human disease
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Placental PFAS concentrations are associated with perturbations of placental DNA methylation
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- Authors
- Svoboda, L. K., Ishikawa, T., & Dolinoy, D. C.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Svoboda, Laurie K
- Venue
- Environmental Epigenetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-01-01
- Volume
- 8
- Issue
- 1
- Pages
- dvac017-dvac017
- ISSN
- 1674-5507 (ISSN-L)
- 2058-5888
- PMC
- PMC9600458
- OpenAlex
- W4300862062
- Cited by
- 27
- References
- 264
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 7 · 2023: 4
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Current Zoology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Environmental Health Sciences (5K01ES032048, ES017885, ES026697, R35ES031686, T32ES007062)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Health, Environment, Cognitive Aging
- Keywords
- developmental toxicants, cardiovascular disease, sex differences, epigenetic programming, transgenerational effects, lead exposure, phthalates, perfluorinated compounds, environmental pollutants, sexual dimorphism, life course
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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