Effect of prenatal exposure to phthalates on epigenome-wide DNA methylations in cord blood and implications for fetal growth: The Hokkaido Study on Environment and Children's Health | Health & Environmental Research Online (HERO)

HERO ID

8397118

Reference Type

Journal Article

Title

Effect of prenatal exposure to phthalates on epigenome-wide DNA methylations in cord blood and implications for fetal growth: The Hokkaido Study on Environment and Children's Health

Author(s)

Miura, R; Ikeda-Araki, A; Ishihara, T; Miyake, K; Miyashita, C; Nakajima, T; Kobayashi, S; Ishizuka, M; Kubota, T; Kishi, R; ,

Year

2021

Is Peer Reviewed?

1

Journal

Science of the Total Environment
ISSN: 0048-9697
EISSN: 1879-1026

Publisher

ELSEVIER

Location

AMSTERDAM

Volume

783

Page Numbers

147035

Language

English

PMID

33872906

DOI

10.1016/j.scitotenv.2021.147035

Web of Science Id

WOS:000656998600015

URL

https://linkinghub.elsevier.com/retrieve/pii/S0048969721021057
Exit

Abstract

Prenatal exposure to phthalates negatively affects the offspring's health. In particular, epigenetic alterations, such as DNA methylation, may connect phthalate exposure with health outcomes. Here, we evaluated the association of di-2-ethylhexyl phthalate (DEHP) exposure in utero with cord blood epigenome-wide DNA methylation in 203 mother-child pairs enrolled in the Hokkaido Study on Environment and Children's Health, using the Illumina HumanMethylation450 BeadChip. Epigenome-wide association analysis demonstrated the predominant positive associations between the levels of the primary metabolite of DEHP, mono(2-ethylhexyl) phthalate (MEHP), in maternal blood and DNA methylation levels in cord blood. The genes annotated to the CpGs positively associated with MEHP levels were enriched for pathways related to metabolism, the endocrine system, and signal transduction. Among them, methylation levels of CpGs involved in metabolism were inversely associated with the offspring's ponderal index (PI). Further, clustering and mediation analyses suggested that multiple increased methylation changes may jointly mediate the association of DEHP exposure in utero with the offspring's PI at birth. Although further studies are required to assess the impact of these changes, this study suggests that differential DNA methylation may link phthalate exposure in utero to fetal growth and further imply that DNA methylation has predictive value for the offspring's obesity.

Keywords

DEHP; EWAS; Increased methylation; MEHP; Ponderal index; Alkylation; Blood; DNA; Health; Metabolism; Metabolites; Methylation; Signal transduction; Cord blood; Di(2-ethylhexyl)phthalate; DNA Methylation; Epigenomes; EWAS; Increased methylation; Mono-(2-ethylhexyl)phthalate; Phthalate exposures; Ponderal index; Prenatal exposure; Esters; phthalic acid; phthalic acid bis(2 ethylhexyl) ester; phthalic acid; phthalic acid bis(2 ethylhexyl) ester; phthalic acid derivative; blood; child health; DNA; gene; metabolism; metabolite; methylation; phthalate; adult; Article; CpG island; DNA methylation; environmental monitoring; epigenetics; epigenome; female; fetus; fetus growth; gene ontology; human; male; newborn; prenatal exposure; progeny; sex ratio; signal transduction; umbilical cord blood; child; child health; DNA methylation; fetus blood; fetus development; genetics; pregnancy; Child; Child Health; Diethylhexyl Phthalate; DNA Methylation; Epigenome; Female; Fetal Blood; Fetal Development; Humans; Infant, Newborn; Phthalic Acids; Pregnancy; Prenatal Exposure Delayed Effects