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Open AccessArticle

Prenatal Exposure to Arsenic and Cadmium Impacts Infectious Disease-Related Genes within the Glucocorticoid Receptor Signal Transduction Pathway

1
Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, 135 Dauer Drive, CB 7431, Chapel Hill, NC 27599, USA
2
Curriculum in Toxicology, School of Medicine, University of North Carolina, 104 Mason Farm Road, CB 7310, Chapel Hill, NC 27599, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2014, 15(12), 22374-22391; https://doi.org/10.3390/ijms151222374
Received: 29 August 2014 / Revised: 4 November 2014 / Accepted: 26 November 2014 / Published: 3 December 2014
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells 2014)
There is increasing evidence that environmental agents mediate susceptibility to infectious disease. Studies support the impact of prenatal/early life exposure to the environmental metals inorganic arsenic (iAs) and cadmium (Cd) on increased risk for susceptibility to infection. The specific biological mechanisms that underlie such exposure-mediated effects remain understudied. This research aimed to identify key genes/signal transduction pathways that associate prenatal exposure to these toxic metals with changes in infectious disease susceptibility using a Comparative Genomic Enrichment Method (CGEM). Using CGEM an infectious disease gene (IDG) database was developed comprising 1085 genes with known roles in viral, bacterial, and parasitic disease pathways. Subsequently, datasets collected from human pregnancy cohorts exposed to iAs or Cd were examined in relationship to the IDGs, specifically focusing on data representing epigenetic modifications (5-methyl cytosine), genomic perturbations (mRNA expression), and proteomic shifts (protein expression). A set of 82 infection and exposure-related genes was identified and found to be enriched for their role in the glucocorticoid receptor signal transduction pathway. Given their common identification across numerous human cohorts and their known toxicological role in disease, the identified genes within the glucocorticoid signal transduction pathway may underlie altered infectious disease susceptibility associated with prenatal exposures to the toxic metals iAs and Cd in humans. View Full-Text
Keywords: arsenic; cadmium; environmental toxicant; epigenome; genome; glucocorticoid receptor; infectious disease; in utero; pathway; signal transduction arsenic; cadmium; environmental toxicant; epigenome; genome; glucocorticoid receptor; infectious disease; in utero; pathway; signal transduction
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Rager, J.E.; Yosim, A.; Fry, R.C. Prenatal Exposure to Arsenic and Cadmium Impacts Infectious Disease-Related Genes within the Glucocorticoid Receptor Signal Transduction Pathway. Int. J. Mol. Sci. 2014, 15, 22374-22391.

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