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

Abstract

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.

Keywords: birth cohort; environmental pollutants; epigenetics; microRNA; placenta.

Figures

Figure 1.

Study Design.

Figure 2.

Influence of PBDE congeners on placental miRNA profile (n = 104). (A) Association between let-7c and PBDE 99 (B) Association between miR-188–5p and PBDE 209. Error bars represent standard error interval. P-value is based on generalized linear model.

Figure 3.

Influence of PCB congeners on placental miRNA profile (n = 105). (A) Association between miR-1537 and PCB 52 (B) Association between miR-1537 and PCB 101 (C) Association between miR-1537 and total PCB. Error bars represent standard error interval. P-value is based on generalized linear model.

Figure 4.

miRNAs significantly differentially expressed due to toxic metal exposure (n = 43). (A) Hg (B) Pd (C) Cd. Circle/triangle and error bar represent mean and standard error, respectively.