Mirna Expression in the Cervix Is Associated with Lead and Mercury Exposure during Pregnancy

Abstract

Mirna Expression in the Cervix Is Associated with Lead and Mercury Exposure during PregnancyAbstract Number:2550 Alison Sanders*, Heather Burris, Allan Just, Katherine Svensson, Chitra Amarasiriwardena, Valeria Motta, Adriana Mercado-Garcia, Joel Schwartz, Martha Tellez-Rojo, Robert Wright, and Andrea Baccarelli Alison Sanders* Icahn School of Medicine at Mount Sinai, United States, E-mail Address: [email protected] Search for more papers by this author , Heather Burris Beth Isreal Deaconess Medical Center, Harvard Medical School, United States, E-mail Address: [email protected] Search for more papers by this author , Allan Just Harvard School of Public Health, United States, E-mail Address: [email protected] Search for more papers by this author , Katherine Svensson Icahn School of Medicine at Mount Sinai, United States, E-mail Address: [email protected] Search for more papers by this author , Chitra Amarasiriwardena Icahn School of Medicine at Mount Sinai, United States, E-mail Address: [email protected] Search for more papers by this author , Valeria Motta Harvard School of Public Health, United States, E-mail Address: [email protected] Search for more papers by this author , Adriana Mercado-Garcia National Institute of Public Health , Mexico, E-mail Address: [email protected] Search for more papers by this author , Joel Schwartz Harvard School of Public Health, United States, E-mail Address: [email protected] Search for more papers by this author , Martha Tellez-Rojo National Institute of Public Health , Mexico, E-mail Address: [email protected] Search for more papers by this author , Robert Wright Icahn School of Medicine at Mount Sinai, United States, E-mail Address: [email protected] Search for more papers by this author , and Andrea Baccarelli Harvard School of Public Health, United States, E-mail Address: [email protected] Search for more papers by this author AbstractToxic metals including lead (Pb) and mercury (Hg) are associated with adverse pregnancy outcomes. miRNAs are small non-coding RNAs that post-transcriptionally control gene expression. miRNAs are particularly susceptible to environmental exposures, and no previous studies have examined environmentally-associated alterations in cervix miRNA expression during pregnancy. This study aimed to analyze the association between miRNA expression in the cervix with Pb and Hg levels biomonitored during pregnancy. We obtained cervical swabs from 80 women between 18 to 20 weeks gestation in a cohort from Mexico City, Mexico. Cervical RNA was extracted and miRNA expression was quantified in a subset of 60 samples using the nCounter Analysis System from Nanostring. Women’s blood Pb was analyzed via ICP-MS and toenail Hg levels were analyzed with a direct Hg analyzer. We performed linear regression to examine the associations between expression of thirty-five miRNAs and metal exposures adjusting for women’s age, education, and environmental tobacco smoke. Expression of miR-188 was positively associated with maternal blood Pb levels (ß=0.3, p=0.04). Expression of let-7b (ß=-1.9, p=0.02), miR-205 (ß=-2.9, p=0.02), and miR-203 (ß=-2.3, p=0.03) were negatively associated with toenail Hg levels, whereas expression of miR-1283 (ß=1.4, p=0.01) and miR-888 (ß=1.0, p=0.03) were positively associated. Pathway analysis of the five Hg-associated miRNAs revealed enrichment for genes involved in cell cycle, cancer, and organismal injury and abnormalities (p=1x10-11). Notably, let-7, miR-205, and miR-203 are known to play a role in reproductive system diseases. We showed altered miRNA expression in the human cervix during pregnancy associated with biomonitored toxic metal levels. These findings highlight miRNAs as novel responders to maternal chemical exposure in specific tissues relevant to labor. The role of metals and cervical miRNA expression in pregnancy outcomes deserves further study.