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

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.

The Role of Placental DNA Methylation at Reproduction-Related Genes in Associations between Prenatal Bisphenol Analogues Exposure and the Digit Ratio in Children at Age 4: A Birth Cohort Study

“…The associations between prenatal exposure to BPF and BPAF and 4-year-old children’s digit ratios remained significant in a smaller population in this study compared with our previous one (345 vs 545), suggesting the robustness of the feminizing effects of specific BPs. Recent studies have explored the role of DNAm between prenatal BPs exposure and children’s health, most of which measured DNAm in cord blood, peripheral blood, or other tissues of children. − Placental DNAm, however, is more sensitive to EDC exposure with unique hypomethylated patterns . In this study, we found significant associations between prenatal BPF exposure and increased placental DNAm at FGF13 , and the hypermethylation of FGF13 was further associated with increased digit ratios in children at 4 years of age.…”

Sex-Specific and Trimester-Specific Associations of Prenatal Exposure to Bisphenols, Parabens, and Triclosan with Neonatal Birth Size and Gestational Age

“…Finally, 127 pregnant women were excluded for lacking important covariate information and birth outcome data, and a total of 483 mother-child pairs were included in the final analyses. Low birth weight and preterm birth were defined as newborns with a birth weight <2500 g and gestational age at birth <37 completed weeks, respectively.…”

“…Despite no definitive mechanism to explain the effects of EDCs on birth outcomes, animal and epidemiological studies have demonstrated that exposure to bisphenols, parabens, and TCS is related to altered hormones (estrogen and thyroid-stimulating hormones), elevated levels of oxidative stress, and disturbances in lipid metabolism . Emerging evidence also suggests that DNA methylation and epigenetic changes induced by EDCs may help explain the adverse effects of intrauterine exposure to EDCs on placental function and fetal development. , It is well established that EDC levels in maternal serum and cord blood are highly relevant, implying that maternal EDC levels can be a signal for intrauterine exposure to some extent . In view of the short half-life of target EDCs and the poor reproducibility of urine, serum is more suitable for EDC exposure assessment and is capable of reducing the bias in the exposure assay …”

Epigenetic studies in children at risk of stunting and their parents in India, Indonesia and Senegal: a UKRI GCRF Action Against Stunting Hub protocol paper

“…Epigenetics represents the distillation and integration of the exposures and the biological response implicated in stunting. Epigenetic regulation is essential for neurogenesis, brain function and behaviour, [4][5][6][7] it affects in-utero and postnatal growth, [8][9][10] it is central to nutritional metabolism [9][10][11][12][13][14] and immune function, 15 it responds to a wide range of environmental exposures, [16][17][18] and it determines longevity and the health trajectory across the life-course. [19][20][21] Stunting often begins before birth and there is a recurrent intergenerational component whereby women who were themselves stunted in childhood are at greater risk of bearing stunted offspring.…”