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# Pregnancy exposure to phthalates and placental DNA methylation in the French EDEN cohort

Paulina Jedynak, Jörg Tost, Ekaterina Bourova Flin, Florence Busato, Anne

Forhan, Barbara Heude, Milan Jakobi, Sophie Rousseaux, Joel Schwartz,

Rémy Slama, et al.

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## ► To cite this version:

Paulina Jedynak, Jörg Tost, Ekaterina Bourova Flin, Florence Busato, Anne Forhan, et al. Pregnancy exposure to phthalates and placental DNA methylation in the French EDEN cohort. ISEE 2021 - 33rd Annual Conference of the International Society of Environmental Epidemiology, Aug 2021, Virtual conference, France. 10.1289/isee.2021.O-TO-048. hal-04987926

HAL Id: hal-04987926

https://hal.science/hal-04987926v1

Submitted on 12 Mar 2025

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BACKGROUND AND AIM: Foetal growth and development strongly depend upon the health of the placenta. Prenatal exposure to phthalates has been hypothesized to be associated with differential DNA methylation, however epigenome-wide studies on placental tissue are lacking. The aim of this study was to characterize associations between pregnancy urinary concentrations of phthalate metabolites and placental DNA methylation. METHODS: We measured concentrations of 11 phthalate metabolites in maternal spot urine samples collected between 22-29 gestational weeks in 202 mother-son pairs. We analysed DNA methylation levels in term placental tissue using IlluminaHM450 BeadChips. We performed an adjusted epigenome-wide association study (EWAS) and identified differentially methylated regions (DMRs, ≥ 5 CpGs). We also evaluated DNA methylation of repetitive elements Alu and LINE-1. RESULTS: We identified 6 DMRs associated with urinary concentrations of phthalate metabolites. Monoethyl phthalate (MEP) was positively associated with 2 DMRs encompassing imprinted genes (SGCE/PEG10) and a gene involved in the immunological response (GCA). Other positive associations were detected for: monocarboxy-iso-nonyl-phthalate (MCNP) and HSPA1A/HSPA1L genes encoding heat shock proteins; mono(3-carboxypropyl)-phthalate (MCPP) and ART5 encoding protein responsible for protein function regulation; mono-iso-buthyl-phthalate (MiBP) and transcription factor coding REPIN1 gene. The only negative association was identified between mono(2-ethylhexyl)-phthalate (MEHP) exposure and DMR encompassing transcription factor coding ZSCAN16 gene. Finally, we found that pregnancy monobenzyl phthalate concentrations were negatively associated with placental methylation of Alu repeats. CONCLUSIONS: Our study is the first one to describe the genome-wide epigenetic modifications of placental DNA in association with pregnancy exposure to phthalates. Some phthalates may be associated with differential methylation of placental DNA, including changes in repetitive element methylation. Interestingly, 1 of the 5 highlighted phthalate metabolites has been associated with the placental-to-foetal weight ratio in a previous study relying on EDEN cohort. KEYWORDS: Phthalates, Endocrine disrupting chemicals, Chemical exposures, Birth outcomes, Epigenomics