In utero exposures to environmental organic pollutants disrupt epigenetic marks linked to fetoplacental development.

While the developing fetus is largely shielded from the external environment through the protective barrier provided by the placenta, it is increasingly appreciated that environmental agents are able to cross and even accumulate in this vital organ for fetal development. To examine the potential influence of environmental pollutants on the placenta, we assessed the relationship between polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and several epigenetic marks linked to fetoplacental development. We measured IGF2/H19 imprint control region methylation, IGF2 and H19 expression, IGF2 loss of imprinting (LOI) and global DNA methylation levels in placenta (n = 116) collected in a formative research project of the National Children's Study to explore the relationship between these epigenetic marks and the selected organic environmental pollutants. A positive association was observed between global DNA methylation and total PBDE levels (P <0.01) and between H19 expression and total PCB levels (P = 0.04). These findings suggest that differences in specific epigenetic marks linked to fetoplacental development occur in association with some, but not all, measured environmental exposures.

Exploring the associations between microRNA expression profiles and environmental pollutants in human placenta from the National Children's Study (NCS).

The placenta is the principal regulator of the in utero environment, and disruptions to this environment can result in adverse offspring health outcomes. To better characterize the impact of in utero perturbations, we assessed the influence of known environmental pollutants on the expression of microRNA (miRNA) in placental samples collected from the National Children's Study (NCS) Vanguard birth cohort. This study analyzed the expression of 654 miRNAs in 110 term placentas. Environmental pollutants measured in these placentas included dichlorodiphenyldichloroethylene (DDE), bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd). A moderated t-test was used to identify a panel of differentially expressed miRNAs, which were further analyzed using generalized linear models. We observed 112 miRNAs consistently expressed in >70% of the samples. Consistent with the literature, miRNAs located within the imprinted placenta-specific C19MC cluster, specifically mir-517a, mir-517c, mir-522, and mir-23a, are among the top expressed miRNA in our study. We observed a positive association between PBDE 209 and miR-188-5p and an inverse association between PBDE 99 and let-7c. Both PCBs and Cd were positively associated with miR-1537 expression level. In addition, multiple let-7 family members were downregulated with increasing levels of Hg and Pb. We did not observe DDE or BPA levels to be associated with placental miRNA expression. This is the first birth cohort study linking environmental pollutants and placental expression of miRNAs. Our results suggest that placental miRNA profiles may signal in utero exposures to environmental chemicals.

Selected persistent organic pollutants in human placental tissue from the United States.

Emerging and legacy environmental pollutants such as polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and organochlorine pesticide metabolite DDE are found in human placenta, indicating prenatal exposure, but data from the United States are sparse. We sought to determine concentrations of these compounds in human placentae as part of a formative research project conducted by the National Children's Study Placenta Consortium. A total of 169 tissue specimens were collected at different time points post delivery from 43 human placentae at three U.S. locations, and analyzed by gas chromatography coupled with mass spectrometry following extraction using matrix solid phase dispersion. PBDEs, PCBs, and DDE were detected in all specimens. The concentrations of 10 PBDEs (Σ10PBDEs), 32 PCBs (Σ32PCBs) and p,p'-DDE were 43-1723, 76-856 and 10-1968pgg(-1) wet weight, respectively, in specimens collected shortly after delivery. Significant geographic differences in PBDEs were observed, with higher concentrations in placentae collected in Davis, CA than in those from Rochester, NY or Milwaukee, WI. We combined these with other published data and noted first-order declining trends for placental PCB and DDE concentrations over the past decades, with half-lives of about 5 and 8years, respectively. The effect of time to tissue collection from refrigerated placentae on measured concentrations of these three classes of persistent organic pollutants was additionally examined, with no significant effect observed up to 120h. The results of this work indicate that widespread prenatal exposure to persistent organic pollutants in the United States continues.