Association of in utero exposure to phthalate and DINCH metabolites with placental DNA methylation.
Por:
Vespalcova H, Knox B, Sakhi AK, Thomsen C, Aguilar-Lacasaña S, Cosin-Tomas M, Gómez-Herrera L, Sánchez García O, Llurba E, Gómez-Roig MD, Sunyer J, Dadvand P, Bustamante M and Vrijheid M
Publicada:
1 dic 2025
Ahead of Print:
19 nov 2025
Resumen:
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.
Filiaciones:
Vespalcova H:
ISGlobal, Barcelona, Spain
Universitat Pompeu Fabra (UPF), Barcelona, Spain
Knox B:
ISGlobal, Barcelona, Spain
Universitat Pompeu Fabra (UPF), Barcelona, Spain
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
Sakhi AK:
Department of Food Safety, Norwegian Institute of Public Health, Oslo, Norway
Thomsen C:
Department of Food Safety, Norwegian Institute of Public Health, Oslo, Norway
Aguilar-Lacasaña S:
ISGlobal, Barcelona, Spain
Universitat Pompeu Fabra (UPF), Barcelona, Spain
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
Cosin-Tomas M:
ISGlobal, Barcelona, Spain
Universitat Pompeu Fabra (UPF), Barcelona, Spain
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
Gómez-Herrera L:
ISGlobal, Barcelona, Spain
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
Facultat de Medicina, Universitat de Barcelona (UB), Barcelona, Spain
Sánchez García O:
Department of Obstetrics and Gynaecology, Institut de Recerca (IR SANT PAU). Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Primary Care Interventions to Prevent Maternal and Child Chronic Diseases of Perinatal and Developmental Origin Network (RICORS-SAMID), RD21/0012/0001, Instituto de Salud Carlos III, Madrid, Spain
Llurba E:
Department of Obstetrics and Gynaecology, Institut de Recerca (IR SANT PAU). Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Primary Care Interventions to Prevent Maternal and Child Chronic Diseases of Perinatal and Developmental Origin Network (RICORS-SAMID), RD21/0012/0001, Instituto de Salud Carlos III, Madrid, Spain
Gómez-Roig MD:
BCNatal, Fetal Medicine Research Center, Hospital Sant Joan de Déu and Hospital Clínic, University of Barcelona, Barcelona, Spain
Primary Care Interventions to Prevent Maternal and Child Chronic Diseases of Perinatal and Developmental Origin Network (RICORS-SAMID), RD21/0012/0003, Instituto de Salud Carlos III, Madrid, Spain
Institut de Recerca Sant Joan de Déu, Barcelona, Spain
Sunyer J:
ISGlobal, Barcelona, Spain
Universitat Pompeu Fabra (UPF), Barcelona, Spain
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
IMIM (Hospital del Mar Medical Research Institute), Barcelona, Catalonia, Spain
Dadvand P:
ISGlobal, Barcelona, Spain
Universitat Pompeu Fabra (UPF), Barcelona, Spain
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
Bustamante M:
ISGlobal, Barcelona, Spain
Universitat Pompeu Fabra (UPF), Barcelona, Spain
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
Vrijheid M:
ISGlobal, Barcelona, Spain
Universitat Pompeu Fabra (UPF), Barcelona, Spain
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
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