Prenatal Bisphenol a Exposure, DNA Methylation, and Low Birth Weight: A Pilot Study in Taiwan.

Yu-Fang Huang,Chian-Feng Chen,I-Hsuan Lin,Ming-Song Tsai,Yu-Chao Wang,Chia-Huang Chang,Yen-An Tsai,Wei-Yun Huang,Mei-Lien Chen,Pei-Jung Chen

doi:10.3390/ijerph18116144

Abstract

Prenatal exposure to bisphenol A (BPA) may increase the risk of abnormal birth outcomes, and DNA methylation might mediate these adverse effects. This study aimed to investigate the effects of maternal BPA exposure on maternal and fetal DNA methylation levels and explore whether epigenetic changes are related to the associations between BPA and low birth weight. We collected urine and blood samples originating from 162 mother-infant pairs in a Taiwanese cohort study. We measured DNA methylation using the Illumina Infinium HumanMethylation 450 BeadChip in 34 maternal blood samples with high and low BPA levels based on the 75th percentile level (9.5 μg/g creatinine). Eighty-seven CpGs with the most differentially methylated probes possibly interacting with BPA exposure or birth weight were selected using two multiple regression models. Ingenuity pathway analysis (IPA) was utilized to narrow down 18 candidate CpGs related to disease categories, including developmental disorders, skeletal and muscular disorders, skeletal and muscular system development, metabolic diseases, and lipid metabolism. We then validated these genes by pyrosequencing, and 8 CpGs met the primer design score requirements in 82 cord blood samples. The associations among low birth weight, BPA exposure, and DNA methylation were analyzed. Exposure to BPA was associated with low birth weight. Analysis of the epigenome-wide findings did not show significant associations between BPA and DNA methylation in cord blood of the 8 CpGs. However, the adjusted odds ratio for the dehydrogenase/reductase member 9 (DHRS9) gene, at the 2nd CG site, in the hypermethylated group was significantly associated with low birth weight. These results support a role of BPA, and possibly DHRS9 methylation, in fetal growth. However, additional studies with larger sample sizes are warranted.

Highlights

Accumulating evidence from animal and epidemiological studies has implied that the in utero and early-life environments play critical roles in a variety of adverse health outcomes [1]
To identify the differential methylated CpGs, two multivariate linear regression models were applied to find epigenome-wide significant associations between bisphenol A (BPA) exposure and maternal DNA
We found significant associations between BPA in the second trimester, which represents a critical window of susceptibility for fetal development [7], and low birth weight, and between dehydrogenase/reductase member 9 (DHRS9) methylation in cord blood and low birth weight

Summary

Introduction

Accumulating evidence from animal and epidemiological studies has implied that the in utero and early-life environments play critical roles in a variety of adverse health outcomes [1]. This observation derives from the developmental origins of health and disease (DOHaD) hypothesis (i.e., Barker’s hypothesis), stating that the intrauterine environment can “program” the fetus to disease predisposition later in life by making subtle changes in organ structure or function [2]. Growing evidence suggests that epigenetic mechanisms play a crucial role in modulating exposure-disease relationships [11].

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Results

Conclusion