Title: Influence of in utero Metal Mixture Exposure on the Human Placental Gene Network and Fetal Growth
Speaker: Maya Deyssenroth, PhD
Postdoctoral Fellow, Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai
Abstract:
Fetal growth restriction has implications for health outcomes later in life, including energy balance dysregulation and neurobehavioral dysfunction. Studies, including our own, have shown that disruptions in specific genes (e.g., imprinted genes) in the placenta as well as environmental insults (e.g., metal toxicants) are associated with abnormal fetal growth. However, focusing on the independent effects of individual metals and genes fails to account for the complex interactions that likely exist among individual constituents in both multi-pollutant exposure settings as well as genomic networks. In this study, we assessed metal mixture levels using weighted quantile sum (WQS) regression analysis and profiled the placental transcriptomic network using weighted gene coexpression network analysis (WGCNA) to delineate a fetal growth restriction-related gene-environment signature in the Rhode Island Child Health Study. We identified a metal mixture index predominated by arsenic and cadmium that was significantly, positively associated with fetal-growth restriction. One placental network module enriched for genes functionally related to gene expression processes (GO:0010467) was significantly, inversely associated with fetal growth restriction. The fetal growth-associated metal mixture index was additionally significantly and inversely associated with the fetal growth-associated placental gene network module. Out of the 10 gene expression module hub genes, 5 genes (ANKRD12, C21orf91, INO80D, MBTD1 and PHIP) were significantly, inversely associated with both fetal growth restriction and the As-predominated metal mixture index. This study provides the first comprehensive assessment of the influence of in utero environmental insults on fetal growth through placental genomics. Our findings suggest a combined additive effect of arsenic and cadmium on the downregulation of fetal growth, and this effect may be partially mediated by the downregulation of a network of gene expression-related genes in the placenta.
Date: April 27th, 2017
Time: 12:00-1:00pm
Location: CAM Building, 17 East 102nd Street, West Tower Elevator, 5th Floor, D5-122
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*Light lunch will be provided
