Titre :

Epigenetic footprints: Investigating placental DNA methylation in the context of prenatal exposure to phenols and phthalates

Auteur(s) :

Jedynak, Paulina [Auteur]
Siroux, Valérie [Auteur]
Broséus, Lucile [Auteur]
Tost, Jörg [Auteur]
Busato, Florence [Auteur]
Gabet, Stephan [Auteur]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Thomsen, Cathrine [Auteur]
Sakhi, Amrit K [Auteur]
Sabaredzovic, Azemira [Auteur]
Lyon-Caen, Sarah [Auteur]
Bayat, Sam [Auteur]
Slama, Rémy [Auteur]
Philippat, Claire [Auteur]
Université Grenoble Alpes [UGA]
Lepeule, Johanna [Auteur]

Titre de la revue :

Environment International

Numéro :

189

Pagination :

108763

Éditeur :

Elsevier

Date de publication :

2024-05-28

ISSN :

0160-4120

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Background: Endocrine disrupting compounds (EDCs) such as phthalates and phenols can affect placental functioning and fetal health, potentially via epigenetic modifications. We investigated the associations between pregnancy ...
Lire la suite >Background: Endocrine disrupting compounds (EDCs) such as phthalates and phenols can affect placental functioning and fetal health, potentially via epigenetic modifications. We investigated the associations between pregnancy exposure to synthetic phenols and phthalates estimated from repeated urine sampling and genome wide placental DNA methylation. Methods: The study is based on 387 women with placental DNA methylation assessed with Infinium MethylationEPIC arrays and with 7 phenols, 13 phthalates, and two non-phthalate plasticizer metabolites measured in pools of urine samples collected twice during pregnancy. We conducted an exploratory analysis on individual CpGs (EWAS) and differentially methylated regions (DMRs) as well as a candidate analysis focusing on 20 previously identified CpGs. Sex-stratified analyses were also performed. Results: In the exploratory analysis, when both sexes were studied together no association was observed in the EWAS. In the sex-stratified analysis, 114 individual CpGs (68 in males, 46 in females) were differentially methylated, encompassing 74 genes (36 for males and 38 for females). We additionally identified 28 DMRs in the entire cohort, 40 for females and 42 for males. Associations were mostly positive (for DMRs: 93% positive associations in the entire cohort, 60% in the sex-stratified analysis), with the exception of several associations for bisphenols and DINCH metabolites that were negative. Biomarkers associated with most DMRs were parabens, DEHP, and DiNP metabolite concentrations. Some DMRs encompassed imprinted genes including APC (associated with parabens and DiNP metabolites), GNAS (bisphenols), ZIM2;PEG3;MIMT1 (parabens, monoethyl phthalate), and SGCE;PEG10 (parabens, DINCH metabolites). Terms related to adiposity, lipid and glucose metabolism, and cardiovascular function were among the enriched phenotypes associated with differentially methylated CpGs. The candidate analysis identified one CpG mapping to imprinted LGALS8 gene, negatively associated with ethylparaben. Conclusions: By combining improved exposure assessment and extensive placental epigenome coverage, we identified several novel genes associated with the exposure, possibly in a sex-specific manner.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CHU Lille
Institut Pasteur de Lille

Collections :

• IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483

Date de dépôt :

2024-10-31T18:45:48Z
2024-10-31T18:56:08Z
2024-11-06T07:51:19Z