Cited by 27Birth, Development, and HealthEffects and risks of endocrine disrupting chemicalsHealth, Environment, Cognitive Aging

Developmental toxicant exposures and sex-specific effects on epigenetic programming and cardiovascular health across generations

Open access
Svoboda, Laurie K, Ishikawa, Tomoko, Dolinoy, Dana C·2022·Environmental Epigenetics

Abstract

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 measured
  • PFAS exposure has potential generational impacts due to epigenetic changes.

    “with potential generational impacts due to epigenetic changes”

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Research works printed but not linked: 1

  1. [94]Davuljigari CB, Gottipolu RR. Late-life cardiac injury in rats following early life exposure to lead: reversal effect of nutrient metal mixture. Cardiovasc Toxicol 2020; 20: 249– 60. 31541351

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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
Published
2022-01-01
Volume
8
Issue
1
Pages
dvac017-dvac017
ISSN
  • 1674-5507 (ISSN-L)
  • 2058-5888
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
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

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