Environmental pollutants and essential elements as regulators of miR-30b, miR-223 and Let-7a microRNAs expression in maternal sera from the NEHO cohort

Abstract

Background: Birth cohorts of women living in highly industrialized areas provide an ideal setting for studying the correlation between environmental exposure and health. Objectives: To evaluate serum microRNA expression in response to environmental contaminants in 68 healthy pregnant women from the NEHO birth cohort. Methods: Serum contaminants were determined by GC-MS/MS and ICP-MS/MS. Serum microRNA expression was determined by qPCR. Associations between miRNA dCTs and single serum element levels were tested by linear regression models, while whole mixture effect was studied by WQS regression analysis. Results: In separate regression models, a positive association was found between miR-223 dCT and concentrations of Se and Zn, while a negative association between miR-30b and Hg levels was observed. Similar regression models were also conducted using tertiles of each chemical as independent variables. In this setting, the Let-7a dCT was decreased in the comparison between medium and low tertiles of Se. The highest tertiles of Zn and p,p-DDE showed a significant association with increasing levels of miR-223 dCT with respect to the lower tertile; moreover, miR-30b dCT was reduced in the comparison between high and low tertiles of Hg. The observed data were confirmed by fold-change analysis. A WQS analysis built on tertiles of contaminant distribution revealed a significant mixture effect on the expression of the analyzed miRNAs. The inverse association between Let-7a dCT and the WQS index was dominated by Zn, Se, Cu, Hg and HCB. Moreover, miR-223 dCT was positively associated with the WQS index, where p,p-DDE, Zn and Se showed the greatest contributions to the association. Conversely, the reduction of miR-30b dCT was mainly driven by Hg and Se. Discussion: This study allowed us to characterize the role of prolonged exposure to environmental contaminants influencing the expression of circulating miRNAs in the serum of women in the last trimester of pregnancy.