A multipollutant low-grade exposure regulates the expression of miR-30b, Let-7a and miR-223 in maternal sera: evidence from the NEHO cohort

There is growing evidence that environmental pollutants can induce epigenetic modifications altering the balance of miRNAs and inducing the onset of pathological conditions in animals. In this study, we measured the serum concentration of a suite of inorganic and organic pollutants (Cu, Zn, Se, Hg, HCB, p,p'-DDE, PCBs) and their association to serum miR-30b, miR-223 and Let-7a microRNA expression in 68 healthy pregnant women from the NEHO birth cohort sited in a highly industrialized area. The effects of the pollutants on the modulation of circulating miRNAs' expression were first investigated using linear continuous regression models with a single-compound approach showing that miR-223 expression was significantly associated with serum concentration of Se and Zn (pSe= 0.0336; pZn=0.0225) and miR-30b was associated with Hg levels (pHg= 0.019). Furthermore, when contaminants were categorized into tertiles miR-223 and miR-30b showed a positive association with higher tertiles of Zn, p,p'-DDE (pZn=0.023; pDDE=0.041) and Hg (pHg=0.008), respectively. Moreover, Let-7a expression was exclusively influenced by medium tertiles levels of Se (low vs medium tertiles, p=0.001). Simultaneous exposure to multi-pollutant mixture was approached by WQS regression model. Evidence clearly show a driving effect of Zn, Se, Cu, Hg and HCB on significant increased expression of Let-7a. Mercury and Se significantly amplified the expression for miR-30b. Differently, the combined effect of p,p'-DDE, Zn and Se decreased miR-223 expression. The documented modified expression of circulating miRNAs in the serum of pregnant women, exposed to low-medium dose contaminants mixtures offers innovative early-warning approaches to human health risk assessment.