Association of in utero exposure to phthalate and DINCH metabolites with placental DNA methylation

dc.contributor.authorDadvand, Payam
dc.contributor.authorBustamante Pineda, Mariona
dc.contributor.authorVrijheid, Martine
dc.contributor.authorVespalcova, Hana
dc.contributor.authorKnox, Bethany
dc.contributor.authorSakhi, Amrit K.
dc.contributor.authorThomsen, Cathrine
dc.contributor.authorAguilar Lacasaña, Sofía
dc.contributor.authorCosín Tomàs, Marta
dc.contributor.authorGómez-Herrera, Laura
dc.contributor.authorSánchez García, Olga
dc.contributor.authorLlurba Olivé, Elisa
dc.contributor.authorGómez Roig, Ma. Dolores
dc.contributor.authorSunyer, Jordi
dc.date.accessioned2026-01-08T19:10:32Z
dc.date.available2026-01-08T19:10:32Z
dc.date.issued2025-11-19
dc.date.updated2026-01-08T19:10:33Z
dc.description.abstractPhthalates and DINCH are non-persistent chemicals widely used in consumer products. In utero exposure to these compounds has been linked to adverse reproductive and long-term health outcomes, potentially through epigenetic changes in the placenta. This study investigated associations between maternal phthalate and DINCH metabolite levels and placental DNA methylation in 469 mother–child pairs from the Barcelona Life Study Cohort (BiSC). Fifteen phthalate and two DINCH metabolites were measured in pooled maternal urine samples collected at 19 and 35 weeks of gestation using liquid chromatography–tandem mass spectrometry (LC-MS/MS. Placental DNA methylation was assessed using the Illumina EPIC array. We applied robust linear regression models to test associations between single exposures at 19 weeks, 35 weeks, and whole pregnancy (average of the two time points), with each CpG site. In secondary analyses, quantile g-computation was used to test associations between exposure mixtures and suggestive CpGs (p-value < 1E-05). We identified 38 Bonferroni significant associations in the single exposure models (p-value < 1E-07)— 24 at 19 weeks, 8 at 35 weeks and 6 for the whole pregnancy period. Suggestive CpGs (p-value < 1E-05) were annotated to genes involved in metabolic, immune and vascular pathways, steroid biosynthesis, and sex hormone signaling. Sex-stratified analyses revealed 49 female-specific and 42 male-specific associations, most of which were identified at a single time point. Mixture analyses revealed 20 significant associations, all consistent in direction with the single-metabolite models. These results suggest that prenatal exposure to phthalates and DINCH may contribute to placental epigenetic alterations supporting a role for endocrine disruption, metabolism, and vascular and immune modulation in mediating their effects.
dc.format.extent15 p.
dc.format.mimetypeapplication/pdf
dc.identifier.idgrec762249
dc.identifier.issn0160-4120
dc.identifier.pmid41275763
dc.identifier.urihttps://hdl.handle.net/2445/225191
dc.language.isoeng
dc.publisherElsevier Ltd.
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1016/j.envint.2025.109946
dc.relation.ispartofEnvironment International, 2025, num.206
dc.relation.urihttps://doi.org/10.1016/j.envint.2025.109946
dc.rightscc-by-nc-nd (c) Dadvand, Payam et al., 2025
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.classificationMetilació
dc.subject.classificationContaminants
dc.subject.classificationAdults
dc.subject.classificationÀcid ftàlic
dc.subject.otherMethylation
dc.subject.otherPollutants
dc.subject.otherAdulthood
dc.subject.otherPhthalic acid
dc.titleAssociation of in utero exposure to phthalate and DINCH metabolites with placental DNA methylation
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion

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