Placental DNA methylation key topics: Sex- and cell-type specificity, mediation, multi-omics, and biomarker discovery
Open accessAbstract
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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The placenta regulates fetal exposure to inflammatory and oxidative mediators and is frequently sampled in these studies.
“The placenta regulates fetal exposure to inflammatory and oxidative mediators and is frequently sampled in these studies [123,131].”
From Placental Pathophysiology and Developmental Programming of Adult Cardiometabolic Risk: A Narrative Review of Pregnancy Exposures (2026) · cites this paper as [131]
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Wang, Y., Huang, W., Zheng, S., Wang, L., Zhang, L., & Pei, X. (2024) · Scientific Reports · doi:10.1038/s41598-024-52087-3 · Cited by 7 · see citing works
Short history of 5-methylcytosine: from discovery to clinical applications
Taryma‐Leśniak, O., Sokolowska, K. E., & Wojdacz, T. K. (2021) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2020-206922 · Cited by 7 · see citing works
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Self-citationJohnson, N. D., Cutler, D. J., & Conneely, K. N. (2024) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2024.02.009 · Cited by 5 · see citing works
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Environment-induced epigenetic modifications as therapeutic targets for prevention and treatment
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Panteris, E., Kakatsaki, I., Koukou, Z., Kolvatzis, C., Papanikolaou, S., & Hatzidaki, E. (2026) · Pathophysiology · doi:10.3390/pathophysiology33030067
Immune checkpoints TIM-3 and Gal-9 are upregulated in male placentas with acute SARS-CoV-2 infection
Seefried, M., Lurtz, I., Mittelberger, J., Franitza, M., Bubmann, J., Wild, C. M., Ditsch, N. C., Urban, B., Kühn, C., Dannecker, C., et al. (2025) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2025.104797
- 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.
- ORCID
- Venue
- Epigenomics
- Publisher
- Informa UK Limited
- Published
- 2025-07-16
- Volume
- 17
- Issue
- 13
- Pages
- 905-921
- ISSN
- 1750-1911 (ISSN-L)
- 1750-192X
- PMC
- PMC12369625
- OpenAlex
- W4412477310
- Cited by
- 2
- References
- 200
- Citations by year
- 2026: 1 · 2025: 1
- FWCI
- 0.18
- Type
- journal article
- Language
- en
- Open access
- green
- pmc.ncbi.nlm.nih.gov
- 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
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.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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