Abstract
The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations.
Highlights
More than 100 million people around the globe are currently exposed to elevated levels of arsenic that are clearly linked to disease [Uddin and Huda, 2011]
The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort consists of 200 women and their newborns recruited in Gómez Palacio, Mexico
In the present study we focus on miRNA expression analysis coupled with transcriptional profiling utilizing 40 newborn cord blood samples obtained from the larger BEAR cohort
Summary
More than 100 million people around the globe are currently exposed to elevated levels of arsenic that are clearly linked to disease [Uddin and Huda, 2011]. Exposure to arsenic has been associated with a variety of other non-cancer health effects, including adverse effects on memory and intellectual function, heart disease, liver hypertrophy, diabetes, and respiratory system disease [Kapaj et al, 2006]. Inorganic arsenic is known to induce toxic effects on the developing fetus where even modest levels (
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