Cited by 2Epigenetics and DNA MethylationBirth, Development, and HealthGenetic Syndromes and Imprinting

Placental DNA methylation key topics: Sex- and cell-type specificity, mediation, multi-omics, and biomarker discovery

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Cohen, Nathan J., Lesseur, Corina, Cardenas, Andres, Ward-Caviness, Cavin K., Spring, Allison C., Rager, Julia E., Fry, Rebecca C., Eaves, Lauren A.·2025·Epigenomics

Abstract

The placenta is a dynamic organ that serves numerous purposes for fostering a successful pregnancy and the delivery of a healthy infant in humans. It performs critical functions in nutrient and oxygen transport, immune modulation, and hormonal regulation. DNA methylation, a key epigenetic mechanism of transcriptional regulation, plays a key role in the underlying etiologies of placenta-related health complications. Therefore, assessing placental DNA methylation is essential for understanding how adverse prenatal exposures may impact both short-term and long-term health outcomes in women and children. In this review, we summarize current knowledge on the effects of prenatal exposures on placental DNA methylation and their implications for maternal and child health, focused on human population studies. We also outline five critical directions for human placental DNA methylation research: (1) Investigating sex-specific DNA methylation patterns, (2) Assessing cell type-specific DNA methylation signatures, (3) Applying causal inference methods, (4) Integrating multi-omics approaches, and (5) Using DNA methylation as a biomarker for environmental exposures and developmental outcomes. Advancing research in these areas will enhance our understanding of the biological underpinnings of the developmental origins of health and disease (DOHaD) hypothesis and maximize the potential of placental samples to inform DOHaD-related research.

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Crossref · 10.1080/17501911.2025.2533115

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Authors
Cohen, N. J., Lesseur, C., Cardenas, A., Ward-Caviness, C. K., Spring, A. C., Rager, J. E., Fry, R. C., & Eaves, L. A.
Affiliations
  • Icahn School of Medicine at Mount Sinai (US)
  • Stanford University
  • Environmental Protection Agency (US)
  • University of North Carolina at Chapel Hill (US)
Corresponding author
Eaves, Lauren A.
Venue
Epigenomics
Published
2025-07-16
Volume
17
Issue
13
Pages
905-921
ISSN
  • 1750-1911 (ISSN-L)
  • 1750-192X
OpenAlex
W4412477310
Cited by
2
References
200
Citations by year
2026: 1 · 2025: 1
FWCI
0.18
Type
journal article
Language
en
Open access
Locations
  • Epigenomics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
Funders
  • National Institute of General Medical Sciences (R25GM143298)
  • National Institute for Environmental Health Sciences (T32ES007018)
  • Office of the Director (UH3OD023348)
  • National Institute of Child Health and Human Development (RO1HD092374)
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
placental DNA methylation, sex-specific methylation, cell type specificity, causal inference, multi-omics integration, DNA methylation biomarkers, prenatal exposure, developmental origins of health and disease, maternal and child health, placenta, epigenetics
MeSH terms
Multiomics, Female, Humans, Male, Placenta, Pregnancy, Sex Factors, Biomarkers, DNA Methylation, Epigenesis, Genetic, Epigenomics

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