Gestational exposure to perfluoroalkyl substances is associated with placental DNA methylation and birth size

Hexing Wang; Wenyun Li; Jiaqi Yang; Yuanping Wang; Hongyi Du; Minghui Han; Linji Xu; Shuping Liu; Jianping Yi; Yue Chen; Qingwu Jiang; Gengsheng He

doi:10.1016/j.scitotenv.2022.159747

Gestational exposure to perfluoroalkyl substances is associated with placental DNA methylation and birth size

Sci Total Environ. 2023 Feb 1;858(Pt 1):159747. doi: 10.1016/j.scitotenv.2022.159747. Epub 2022 Oct 26.

Authors

Hexing Wang¹, Wenyun Li¹, Jiaqi Yang¹, Yuanping Wang¹, Hongyi Du², Minghui Han², Linji Xu³, Shuping Liu³, Jianping Yi³, Yue Chen⁴, Qingwu Jiang¹, Gengsheng He⁵

Affiliations

¹ School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China.
² Healthy Lifestyle Medical Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ Maternal and Child Health Care Hospital, Tangshan, Hebei province, China.
⁴ School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
⁵ School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China. Electronic address: gshe@shmu.edu.cn.

PMID: 36309289
DOI: 10.1016/j.scitotenv.2022.159747

Abstract

DNA methylation is one potential mechanism for the effects of gestational exposure to perfluoroalkyl substances (PFASs) on fetal growth. We investigated 180 pregnant women who participated in a cohort study conducted in Tangshan City, Northern China, and determined the concentrations of 11 PFASs and the methylation of two genes related to fetal growth [insulin-like growth factor 2 (IGF2) and nuclear receptor subfamily 3 group C member 1 (NR3C1)] and one surrogate marker for global methylation [long interspersed nuclear element-1 (LINE-1)] in placenta tissue. Multiple linear regression analysis was performed to examine the associations of log transformed PFASs with the DNA methylation and birth size. Weighted quantile sum regression was used to determine the mixture effect of PFASs. After adjusting for potential confounders, perfluorooctane sulfonate (PFOS) was negatively associated with the overall methylation of LINE-1. PFASs mixture was negatively associated with the methylation of all CpG loci of LINE-1 and overall methylation of NR3C1. Perfluorootanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and the PFASs mixture showed negative associations with head circumference. After stratified by newborns' sex, PFOA, PFNA and the PFASs mixture was negatively associated with overall methylation of LINE-1 only in the male subgroup and the methylation of all CpG loci of LINE-1 was negatively associated with ponderal index only in the female subgroup. The interaction of newborns' sex with PFOS and PFOA on overall methylation of IGF2 was statistically significant and so was the interaction of sex with PFOS on overall methylation of LINE-1. These findings suggested that intrauterine exposure to PFASs affected placental DNA methylation and reduced fetal growth, which might be modified by sex.

Keywords: DNA methylation; Fetal growth; Mixture exposure; Perfluoroalkyl substances; Placenta; Pregnant women.

MeSH terms

Alkanesulfonic Acids* / toxicity
Cohort Studies
DNA Methylation
Environmental Pollutants* / toxicity
Female
Fluorocarbons* / toxicity
Humans
Infant, Newborn
Male
Placenta
Pregnancy

Substances

perfluorooctane sulfonic acid
Fluorocarbons
Environmental Pollutants
Alkanesulfonic Acids