Bisphenol a Exposure, DNA Methylation, and Asthma in Children

Abstract

Epidemiological studies have reported the relationship between bisphenol A (BPA) exposure and increased prevalence of asthma, but the mechanisms remain unclear. Here, we investigated whether BPA exposure and DNA methylation related to asthma in children. We collected urinary and blood samples from 228 children (Childhood Environment and Allergic Diseases Study cohort) aged 3 years. Thirty-three candidate genes potentially interacting with BPA exposure were selected from a toxicogenomics database. DNA methylation was measured in 22 blood samples with top-high and bottom-low exposures of BPA. Candidate genes with differential methylation levels were validated by qPCR and promoter associated CpG islands have been investigated. Correlations between the methylation percentage and BPA exposure and asthma were analyzed. According to our findings, MAPK1 showed differential methylation and was further investigated in 228 children. Adjusting for confounders, urinary BPA glucuronide (BPAG) level inversely correlated with MAPK1 promoter methylation (β = −0.539, p = 0.010). For the logistic regression analysis, MAPK1 methylation status was dichotomized into higher methylated and lower methylated groups with cut off continuous variable of median of promoter methylation percentage (50%) while performing the analysis. MAPK1 methylation was lower in children with asthma than in children without asthma (mean ± SD; 69.82 ± 5.88% vs. 79.82 ± 5.56%) (p = 0.001). Mediation analysis suggested that MAPK1 methylation acts as a mediation variable between BPA exposure and asthma. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of MAPK1 methylation. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of MAPK1 methylation.

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

“…The DNA methylation levels of 8 CpG sites in cord blood are consistent with those reported in the literature [39,40], and the impact of prenatal BPA exposure on DNA methylation is of great concern. In contrast, previous studies reported that BPA was capable of inducing DNA methylation in both animals [6,41] and humans [15][16][17]40,42]. Hanna et al, (2012) reported that BPA exposure was associated with DNA methylation changes in whole blood using Illumina GoldenGate Methylation Cancer Panel I bead array assays on 1505 CpG sites, in women undergoing ovarian stimulation for in vitro fertilization [15].…”

“…Four animal studies have reported that BPA exposure can provoke intrauterine growth restriction [ 44 ], cause preeclampsia-like features in pregnant mice involved in the reprogramming of DNA methylation of WNT2 (Wnt family member-2) [ 45 ], and cause toxicity in spermatocytes, and DNA methylation may exert an important role in BPA-triggered male reproductive toxicity [ 46 ] and alter the methylation levels of differentially methylated regions (DMRs) including the Snrpn imprinting control region and IGF2R DMR1 [ 47 ]. In addition, three human and epidemiological studies have shown that BPA can cause abnormal development of the central and peripheral nervous system in the fetus [ 48 ], and BPA exposure on children with asthma might operate through the alteration of MAPK1 methylation [ 42 ]. In another epigenome-wide association study on children, being in the high BPA exposure group, compared to the low BPA exposure group, was associated with an increase in DNA methylation of IGF2R [ 14 ].…”

Teratogenicity and toxicity of the new BPA alternative TMBPF, and BPA, BPS, and BPAF in chick embryonic development

“…Indeed, numerous association studies have linked BPA and analogs to human reproductive diseases and disorders including increased miscarriage rates ( Sugiura-Ogasawara et al, 2005 , Zbucka-Kretowska et al, 2018 ), low fetal birth weight ( Huo et al, 2015 ), birth defects such as male hypospadias ( Pallotti et al, 2020 ), endometriosis ( Buck Louis et al, 2013 , Simonelli et al, 2017 ), polycystic ovary syndrome ( Rutkowska and Rachon, 2014 ), breast and prostate cancer ( Jenkins et al, 2009 , Moral et al, 2008 , Shafei et al, 2018 , Zhang et al, 2014 ), and precocious puberty ( Leonardi et al, 2017 ), in addition to many neurological, immune, and metabolic disorders ( Robinson and Miller, 2015 , Kardas et al, 2016 , Thongkorn et al, 2019 , Li et al, 2018 , Tewar et al, 2016 , Legeay and Faure, 2017 , Wang et al, 2012 , Wang et al, 2019 , Yang et al, 2020 , Youssef et al, 2018 ). Further, several large studies have reported that in couples undergoing in vitro fertilization (IVF) there were significant correlations between higher urinary BPA concentrations and reduced sperm counts, and abnormal sperm motility and morphology in men, reduced oocyte yield and peak serum estradiol in women, and reduced success with IVF ( Joint and WHO, 2011 , Matuszczak et al, 2019 , Mok-Lin et al, 2010 ).…”

A review of epigenetic changes in asthma: methylation and acetylation

“…Phthalate exposure could also attenuate the methylation level of TNF-α in whole blood white blood cells and lead to its upregulation, which is an event that increases the risk of asthma in children [89]. The results from another study indicate that exposure to bisphenol A can lead to a decrease in an inflammatory mediator gene MAPK1 methylation in whole blood, provoking childhood asthma [90]. Studies on inner-city children with persistent atopic asthma suggested that persistence in these children was accompanied by promoting the expression of genes related to Th2 immunity.…”