Int J Mol Sci

The placenta is a key organ for fetal and brain development. Its epigenome can be regarded as a biochemical record of the prenatal environment and a potential mechanism of its association with the future health of the fetus. We investigated associations between placental DNA methylation levels and child behavioral and emotional difficulties, assessed at 3 years of age using the Strengths and Difficulties Questionnaire (SDQ) in 441 mother-child dyads from the EDEN cohort. Hypothesis-driven and exploratory analyses (on differentially methylated probes (EWAS) and regions (DMR)) were adjusted for confounders, technical factors, and cell composition estimates, corrected for multiple comparisons, and stratified by child sex. Hypothesis-driven analyses showed an association of cg26703534 () with emotional symptoms, and exploratory analyses identified two probes, cg09126090 (intergenic region) and cg10305789 (), as negatively associated with peer relationship problems, as well as 33 DMRs, mostly positively associated with at least one of the SDQ subscales. Among girls, most associations were seen with emotional difficulties, whereas in boys, DMRs were as much associated with emotional than behavioral difficulties. This study provides the first evidence of associations between placental DNA methylation and child behavioral and emotional difficulties. Our results suggest sex-specific associations and might provide new insights into the mechanisms of neurodevelopment.Exposition prénatale au tabac et à la pollution atmosphérique et effets sur la santé respiratoire et le neurodévelopment de l'enfant: rôle de la méthylation placentaireHorizon 2020 research and innovation programm

Pregnancy exposure to phthalates and synthetic phenols and placental DNA methylation in the SEPAGES cohort

The aim of the present work will be to assess the association between pregnancy phthalates and phenols other than triclosan and DNA methylation of placental genes. We will follow two complementary approaches: 1) Candidate approach: to explore whether associations observed in the EDEN cohort between pregnancy phthalates and phenols other than triclosan and DNA methylation of placental genes can be replicated in the SEPAGES cohort with improved exposure assessment; 2) Exploratory epigenome-wide association study (EWAS) and differentially methylated regions (DMRs) analysis to identify potential new genomic locations affected by phthalates and phenols exposure

Prenatal exposure to triclosan assessed in multiple urine samples and placental DNA methylation

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Associations between prenatal air pollution exposure and placental DNA methylation: a French multi-cohort study

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Pregnancy exposure to phthalates and DNA methylation in male placenta — An epigenome-wide association study

International audienceBackground: Exposure to phthalates during pregnancy may alter DNA methylation in the placenta, a crucial organ for the growth and development of the fetus.Objectives: We studied associations between urinary concentrations of phthalate biomarkers during pregnancy and placental DNA methylation.Methods: We measured concentrations of 11 phthalate metabolites in maternal spot urine samples collected between 22 and 29 gestational weeks in 202 pregnant women. We analyzed DNA methylation levels in placental tissue (fetal side) collected at delivery. We first investigated changes in global DNA methylation of repetitive elements Alu and LINE-1. We then performed an adjusted epigenome-wide association study using IlluminaHM450 BeadChips and identified differentially methylated regions (DMRs) associated with phthalate exposure.Results: Monobenzyl phthalate concentration was inversely associated with placental methylation of Alu repeats. Moreover, all phthalate biomarkers except for monocarboxy-iso-octyl phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate were associated with at least one DMR. All but three DMRs showed increased DNA methylation with increased phthalate exposure. The largest identified DMR (22 CpGs) was positively associated with monocarboxy-iso-nonyl phthalate and encompassed heat shock proteins (HSPA1A, HSPA1L). The remaining DMRs encompassed transcription factors and nucleotide exchange factors, among other genes.Conclusions: This is the first description of genome-wide modifications of placental DNA methylation in association with pregnancy exposure to phthalates. Our results suggest epigenetic mechanisms by which exposure to these compounds could affect fetal development. Of interest, four identified DMRs had been previously associated with maternal smoking, which may suggest particular sensitivity of these genomic regions to the effect of environmental contaminants