Association of in utero exposure to phthalate and DINCH metabolites with placental DNA methylation
Year: 2025
Type: article
Study design: Observational Study
Abstract: Phthalates 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.
Source: Environment International
Institutions: Universitat Pompeu Fabra, Barcelona Institute for Global Health, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Norwegian Institute of Public Health, Universitat de Barcelona, Instituto de Salud Carlos III, Hospital de Sant Pau, Institut de Recerca Sant Pau, Red de Salud Materno Infantil y del Desarrollo, Hospital Sant Joan de Déu Barcelona, Institut de Recerca Sant Joan de Déu, Municipal Institute for Medical Research, Hospital del Mar Research Institute
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $4,750
Funders: Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Joint Programming Initiative A healthy diet for a healthy life, Centres de Recerca de Catalunya, European Commission, Generalitat de Catalunya, Horizon 2020 Framework Programme, European Research Council, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, European Regional Development Fund, Agencia Estatal de Investigación, NextGenerationEU
Awards: Nutrición en el embarazo e infancia y programación de la salud metabólica a través de mecanismos epigenéticos., G1175115578, G1298559095, G1341303, G1433210447, G1491211482, G1622782223, exposomA urbano y crecimiento fetaL: los roles del epigenoMa placentario y la función placentariA (ALMA), G2038104832, G2064873908, G210041235, G2143313326, G2262748287, G2355262757, G2462415295, G2601397997, G2651899972, G2672435700, G2819494518, G2875100122, G288263039, G3005324705, G300979063, G3288897321, G34346518, G3480869486, G3546882995, G3681454997, G3810626647, G4016763146, G4042783231, G4043836026, G410571670, G425668148, G434337789, G4442677895, G451917667, G4526231891, G4704411197, G4749042089, Advancing Tools for Human Early Lifecourse Exposome Research and Translation, G5080475149, G5185833053, G5195188938, G5539308778, G5554424168, G5852091828, G5950656272, G5967599077, G6059375137, G630635040, G630914071, G6453073141, G6656126374, G69051668, G7084143925, G7170678170, G7680012365, G7793665899, G8212248820, G8257616728, G8277360679, G8330114565, G8450998669, G8531209033, G8637226926, G8692663868, G8696694383, G910531720, G929308097
OpenAlex ID: W4416423737