Associations between PBDEs exposure during pregnancy, fetal growth and aberrant DNA methylation of human placenta

Abstract

TPS 711: The exposome, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Aim: To evaluated the association between in utero PBDEs exposure and fetal growth and examined the potential role of altered DNA methylation of growth regulatory genes in these associations. Methods: A total of 249 mother-newborn pairs comprised of 124 fetal growth restriction (FGR) cases and 125 controls within the Wenzhou Birth Cohort were enrolled in this nested case–control study. In utero exposure of 19 PBDEs congeners, including thirteen lower PBDE congeners (BDE-17~190) and six higher brominate BDE congeners (BDE-196~209), were determined by gas chromatography tandem mass spectrometry in umbilical cord blood. Placental DNA methylation of LINE1, HSD11B2 and IGF2 was measured by quantitative polymerase chain reaction-pyrosequencing at differentially methylated regions (DMRs). Multiple linear regression and logistic regressions models were used to examine associations among PBDEs exposure, fetal growth indicators and DMR methylation fractions. Results: Concentrations of BDE-49, BDE-206, BDE-209, BDE-17~190 and ∑19PBDEs were significantly higher in FGR cases than those in normal controls. Meanwhile, DNA methylation of IGF2 and HSD11B2 showed significant differences between FGR group and control group, respectively. BDE-206 (OR: 1.569, 95% CIs: 1.053-2.338), BDE-17~190 (OR: 2.860, 95% CIs: 1.233-6.634), BDE-196~209 (OR: 1.688, 95% CIs: 1.024-2.783) and ∑19PBDEs (OR: 2.387, 95% CIs: 1.220-4.668) concentrations were associated with increased risk of FGR. Being FGR birth were also associated with increasing DNA methylation of HSD11B2 (OR: 1.145, 95% CIs: 1.032-1.270) and decreasing DNA methylation of IGF2 (OR: 0.892, 95% CIs: 0.845, 0.941). In addition, BDE-17~190 showed significant associations with placental DNA methylation of HSD11B2 and IGF2 (β: 1.127, 95% CIs: 0.069-2.186; β: -3.452, 95% CIs: -5.512--1.392). These results were consistent with the expected direction relating PBDEs exposure, fetal growth and placental DNA methylation. Conclusion: We report an inverse association between in utero exposures to PBDEs and fetal growth and provide evidence supporting epigenetic gene plasticity in these associations.