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.

A novel regulatory network among LncRpa, CircRar1, MiR-671 and apoptotic genes promotes lead-induced neuronal cell apoptosis

“…Most research in this area has focused on the role of mRNAs (Soliman et al 2015; Gao et al 2016) or miRNAs (Li et al 2015; Martinez-Pacheco et al 2014), and there is little, if any information on how lncRNAs and circRNAs are involved in lead-induced neurotoxicity. The roles of ncRNAs have been extensively investigated in the context of carcinogenesis and cancer development (Cheng et al 2015).…”

Neuroendocrine disruption in animal models due to exposure to bisphenol A analogues

“…BPA exposure induces DNA methylation and histone protein modifications in the brain and other organs [72; 114; 115; 116; 117; 118; 119; 120; 121]. The expression of miRNAs in the placenta, liver, and likely other organs, including the brain, can also be influenced by BPA [122; 123; 124; 125]. Bisphenols may also induce neuroendocrine disruptive effects by targeting the gut-microbiome-brain axis [126; 127; 128; 129; 130].…”

Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children’s Environmental Health Studies: The Children’s Environmental Health and Disease Prevention Research Center’s Epigenetics Working Group

“…In turn, these changes can manifest later in life and have the capacity to modulate physiological function and susceptibility to disease. Research also is emerging that investigates the placenta as a target tissue by which to study exposures at the maternal–fetal interface (Li Q et al 2015; Maccani and Maccani 2015; Paquette et al 2015; Schroeder and LaSalle 2013). …”