Prenatal bisphenol analogs exposure and placental DNA hypomethylation of genes in the PPAR signaling pathway: Insights for bisphenol analogs' effects on infant anthropometry

Honglei Ji; Haijun Zhu; Ziliang Wang; Hong Liang; Yao Chen; Xiao Liu; Wei Yuan; Qihan Wu; Zhengwei Yuan; Maohua Miao

doi:10.1016/j.envres.2024.120476

Prenatal bisphenol analogs exposure and placental DNA hypomethylation of genes in the PPAR signaling pathway: Insights for bisphenol analogs' effects on infant anthropometry

Environ Res. 2024 Nov 27:120476. doi: 10.1016/j.envres.2024.120476. Online ahead of print.

Authors

Honglei Ji¹, Haijun Zhu¹, Ziliang Wang¹, Hong Liang¹, Yao Chen¹, Xiao Liu², Wei Yuan¹, Qihan Wu¹, Zhengwei Yuan³, Maohua Miao⁴

Affiliations

¹ Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200237, China.
² Hubei Provincial Key Laboratory of Applied Toxicology, National Reference Laboratory of Dioxin, Hubei Provincial Center for Disease Control and Prevention, Wuhan 430079, China.
³ NHC Key Laboratory of Congenital Malformation (Key Laboratory of Health Ministry for Congenital Malformation), Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address: yuanzw@hotmail.com.
⁴ Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200237, China. Electronic address: miaomaohua@live.com.

PMID: 39613017
DOI: 10.1016/j.envres.2024.120476

Abstract

Prenatal exposure to bisphenol analogs (BPs) may pose hazards to offspring's health; however, their underlying mechanisms remain to be elucidated. DNA methylation, a major epigenetic mechanism, may be involved in early programming following environmental disturbances. In this prospective study, we investigated associations between prenatal BPs exposure and the placental DNA methylation levels of 14 candidate genes in the peroxisome proliferator-activated receptor (PPAR) signaling pathway among 205 mother-infant pairs and explored the potential mediating role of the DNA methylation in the association of prenatal BPs exposure with anthropometric measurements of infants aged 1 year. We observed a general pattern that prenatal BPs exposure was associated with the DNA hypomethylation of candidate genes, with associations consistently and notably observed for PPAR α (PPARA), retinoid X receptor α (RXRA), acetyl-CoA acyltransferase 1, and acyl-CoA dehydrogenase medium chain (ACADM) in linear regression and Bayesian kernel machine regression. Both models identified bisphenol F (BPF) as the predominant compound. We found inverse associations between the placental DNA methylation levels of most candidate genes, such as PPARA, RXRA, ACADM, and nuclear receptor subfamily 1 group H member 3 (NR1H3), and the length-for-age z-score, arm circumference-for-age z-score, subscapular skinfold-for-age z-score, and abdominal skinfold thickness of the infants. The DNA methylation levels of RXRA and NR1H3 could mediate the associations between prenatal BPF exposure and increased infant anthropometric measurements, with mediating portions ranging from 23.02% to 30.53%. Our findings shed light on the potential mechanisms underlying the effects of prenatal BPs exposure on infant growth and call for urgent actions for risk assessment and regulation of BPF. Future cohort studies with larger sample sizes are warranted to confirm our findings.

Keywords: BPs; PPAR; epigenetics; infant growth; placenta.