Prenatal Exposure to Arsenic and Cadmium Impacts Infectious Disease-Related Genes within the Glucocorticoid Receptor Signal Transduction Pathway
Published Date:Dec 03 2014
Source:Int J Mol Sci. 2014; 15(12):22374-22391.
Gene Regulatory Networks
Prenatal Exposure Delayed Effects
Reproducibility Of Results
Pubmed Central ID:PMC4284714
Funding:2T42 OH-008673/OH/NIOSH CDC HHS/United States
P30 ES010126/ES/NIEHS NIH HHS/United States
P30-ES010126/ES/NIEHS NIH HHS/United States
P42 ES005948/ES/NIEHS NIH HHS/United States
P42-ES005948/ES/NIEHS NIH HHS/United States
R01-ES019315/ES/NIEHS NIH HHS/United States
Description: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.
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