A team of environmental health researchers has uncovered fresh evidence that chemicals routinely encountered during pregnancy—from combustion byproducts in polluted air to plasticizers in food packaging—may leave measurable chemical tags on the DNA of the placenta and newborn blood cells. The study, published in the open-access journal Epigenetics Communications, is among the relatively few to scan the placental epigenome across both its maternal and fetal sides in relation to a broad panel of non-persistent environmental chemicals, and its findings point to biological pathways that could help explain why gestational exposures have been linked to adverse birth outcomes.
The research, led by Jagadeesh Puvvula of the University of Pennsylvania’s Perelman School of Medicine together with Aimin Chen and collaborators at Brown University, the University of Kentucky, the University of Arkansas for Medical Sciences, the University of Cincinnati, and the U.S. Centers for Disease Control and Prevention, enrolled 75 pregnant individuals who gave birth at the University of Cincinnati Medical Center between August 2014 and September 2017. All participants carried singleton pregnancies, were between 18 and 45 years of age, and were free of major conditions such as diabetes, thyroid disorders, cardiovascular or renal disease, and cancers affecting pregnancy. The cohort was demographically diverse: roughly half of the participants identified as non-Hispanic Black, the median age at delivery was 29 years, and 17 percent reported smoking tobacco during pregnancy. All births were full-term, ranging from 37 to 41 weeks of gestation.
At the delivery visit, the researchers collected 30 milliliters of maternal urine, 10 milliliters of cord blood, and placental tissue from both the maternal and fetal sides of the organ. The urine samples were analyzed for 37 biomarkers spanning four chemical classes: 12 phenols, 13 phthalates, 4 phthalate replacements, and 8 metabolites of polycyclic aromatic hydrocarbons, or PAHs—the compounds formed whenever organic material burns incompletely, whether in vehicle exhaust, grilled food, or tobacco smoke. Phenol and phthalate biomarkers were quantified at the CDC’s National Center for Environmental Health using high-performance liquid chromatography isotope dilution tandem mass spectrometry, while PAH metabolites were measured at NSF International’s Applied Research Center in Ann Arbor, Michigan. Because some chemicals, such as parabens and certain phthalate metabolites, can leach from medical products used during labor and delivery, the team excluded eight biomarkers potentially contaminated by the clinical setting, leaving 29 exposure markers for analysis.
The epigenetic readout relied on the Illumina Infinium HumanMethylation450K BeadChip, an array that interrogates hundreds of thousands of CpG sites—positions in the genome where a cytosine sits next to a guanine and where a methyl group can be attached without altering the underlying DNA sequence. DNA methylation is a cornerstone of epigenetic regulation: it fine-tunes gene activity during development, and shifts in methylation patterns near gene promoters can change how strongly, or whether, a gene is transcribed. After rigorous preprocessing—background correction, dye-bias normalization, beta-mixture quantile normalization, batch-effect removal via an empirical Bayes framework, and exclusion of probes on sex chromosomes or prone to cross-reactivity—the team retained 418,997 CpGs in cord blood mononuclear cells, 415,604 on the fetal side of the placenta, and 412,460 on the maternal side.
A critical technical challenge in methylation studies is that different tissues contain mixtures of cell types, each with its own methylation signature. To disentangle chemistry from cellular composition, the researchers used reference-based deconvolution methods, estimating the proportions of five immune cell types in cord blood—CD8 and CD4 T-lymphocytes, B-cells, natural killer cells, and monocytes—and six cell types in placental tissue, including trophoblasts, syncytiotrophoblast, stromal cells, Hofbauer cells, endothelial cells, and nucleated red blood cells. These estimated proportions were then included as covariates in the statistical models, alongside maternal age, race, education, tobacco use, pre-pregnancy body mass index, and infant sex. Associations were tested with linear regression for 22 biomarkers measured on a continuous scale and with analysis of variance for 7 biomarkers detected in only 20 to 40 percent of participants, with false discovery rate control at a q-value threshold of 0.05 and a genomic inflation factor filter to guard against spurious results.
The headline result was striking in its selectivity. Of the 29 chemical biomarkers assessed, 11—six PAH metabolites, four phthalate-related compounds, and the phenol bisphenol A—showed statistically significant associations with differential CpG methylation in at least one sample type. But when the stricter inflation-factor filter was applied, two compounds emerged as the most consistent signals: 1-hydroxynaphthalene, a metabolite of naphthalene, and mono-3-carboxypropyl phthalate, known as MCPP, a metabolite of certain phthalates. Both were associated with altered methylation in the placenta, and the fetal side of the organ proved the most responsive of the three tissues examined, echoing the placenta’s role as the direct interface between maternal circulation and the developing fetus.
The PAH findings were particularly detailed. Maternal urinary concentrations of 2-hydroxyfluorene were associated with methylation changes at 46 CpG sites on the fetal side of the placenta, many of them hypomethylated and located within 200 base pairs of transcription start sites. Seven of these sites sat in the promoter regions of two genes: ZNF354C, encoding a zinc finger protein, and CCDC63, a coiled-coil domain gene. On the maternal side, 2-hydroxyfluorene and 1-hydroxypyrene were both linked to hypomethylation of CpGs near MFSD2A, a gene that encodes a transporter critical for delivering essential fatty acids across the blood-brain barrier and, in the placenta, for nutrient transfer to the fetus. Twenty-three CpG sites on the fetal side were commonly associated with both PAH metabolites, suggesting a shared mechanistic footprint of combustion-related exposures.
MCPP told a complementary story. Detected-or-not analysis revealed associations with roughly 130 CpGs on the maternal side of the placenta and 69 on the fetal side, with 34 and 15 of those respectively located in transcription start site regions. On the maternal side, four CpGs clustered within 200 base pairs of the promoter of LIG4, a gene essential for DNA ligase IV activity and the non-homologous end-joining pathway that repairs double-strand DNA breaks. On the fetal side, MCPP-associated CpGs mapped near HOOK1, involved in microtubule tethering, and DZIP1, a zinc finger protein implicated in ciliary biology and developmental signaling. Gene set enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes reinforced these themes: CpGs associated with MCPP were enriched for non-homologous end-joining and for neutrophil extracellular trap formation, the latter plausibly connected to a CpG near CSF3, a gene governing granulocyte production.
The pathway analysis for 1-hydroxynaphthalene pointed in a different direction—toward metabolism. On the fetal side of the placenta, enriched pathways included fatty acid biosynthesis, degradation, and metabolism, along with ferroptosis, an iron-dependent form of regulated cell death. Two CpG sites stood out: one near LEPROT/LEPR, the leptin receptor locus long associated with obesity biology, which showed hypomethylation, and one near ACSL5, an acyl-CoA synthetase involved in long-chain fatty acid metabolism, which showed hypermethylation. A sensitivity analysis restricted to the 500 CpGs with the lowest q-values similarly flagged fatty acid metabolism on the maternal side. The authors note that these lipid-related signals align with broader literature linking PAH exposure to metabolic syndrome, cardiovascular conditions, and systemic inflammation, and with prior work showing that prenatal PAH exposure alters methylation of ACSL3 in cord blood, a proposed biomarker for childhood asthma risk.
The researchers are careful to frame the study as exploratory. The sample was modest, exposures were measured at a single delivery-visit time point that may not capture the full gestational window, and the strongly correlated biomarkers within chemical classes raise multicollinearity concerns. The older 450K array also covers fewer type-II probes than newer EPIC platforms, though the authors argue this may have limited false positives given the sample size. No KEGG pathway survived correction at a q-value below 0.1, and the team emphasizes that replication in larger cohorts is essential before drawing clinical conclusions. Still, the study’s contribution is clear: by profiling methylation in both placental sides and cord blood mononuclear cells against a wide panel of phenols, phthalates, and PAHs, it offers a mechanistic bridge between the ubiquitous chemical exposures of modern pregnancy and the developmental programming of newborn health—and it suggests that the placenta, far from being a passive barrier, records an epigenetic diary of the chemical world the mother inhabits. The methylation data have been deposited in NCBI’s Gene Expression Omnibus under accession GSE269983, and the authors call for multi-omics studies integrating exposome, epigenetic, transcriptomic, and phenotype data to fully map the biological pathways at play.
Subject of Research: Associations between gestational exposure to environmental chemicals and DNA methylation changes in the placenta and cord blood mononuclear cells
Article Title: Gestational exposure to environmental chemicals and epigenetic alterations in the placenta and cord blood mononuclear cells
Article References: Puvvula, J., Braun, J. M., DeFranco, E. A., Ho, S.-M., Leung, Y.-K., Huang, S., Zhang, X., Vuong, A. M., Kim, S. S., Percy, Z., Calafat, A. M., Botelho, J. C., & Chen, A. (2024). Gestational exposure to environmental chemicals and epigenetic alterations in the placenta and cord blood mononuclear cells. Epigenetics Communications, 4(1), Article 4. https://doi.org/10.1186/s43682-024-00027-7
Image Credits: AI Generated
DOI: 10.1186/s43682-024-00027-7
Keywords: epigenetics, DNA methylation, placenta, cord blood, phthalates, polycyclic aromatic hydrocarbons, bisphenol A, endocrine disruptors, pregnancy, environmental health, gene enrichment, birth outcomes
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Juliet Wilcox. (October 1, 2026). Everyday Chemicals in Pregnancy Leave Epigenetic Fingerprints on the Placenta, Study Finds. Scienmag. https://scienmag.com/everyday-chemicals-in-pregnancy-leave-epigenetic-fingerprints-on-the-placenta-study-finds/
Juliet Wilcox. “Everyday Chemicals in Pregnancy Leave Epigenetic Fingerprints on the Placenta, Study Finds.” Scienmag, 1 October 2026, https://scienmag.com/everyday-chemicals-in-pregnancy-leave-epigenetic-fingerprints-on-the-placenta-study-finds/. Accessed 1 October 2026.
Juliet Wilcox. “Everyday Chemicals in Pregnancy Leave Epigenetic Fingerprints on the Placenta, Study Finds.” Scienmag. October 1, 2026. https://scienmag.com/everyday-chemicals-in-pregnancy-leave-epigenetic-fingerprints-on-the-placenta-study-finds/
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