A Systems Toxicology-based Approach Reveals Biological Pathways Dysregulated by Prenatal Arsenic Exposure

Background: <a title="Learn more about Prenatal Exposure" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/prenatal-exposure">Prenatal exposure</a> to inorganic arsenic (iAs) is associated with dysregulated fetal gene and protein expression. Potential...

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Main Authors: Jessica E. Laine, Rebecca C. Fry
Format: Article
Language:English
Published: Ubiquity Press 2016-06-01
Series:Annals of Global Health
Subjects:
Online Access:https://annalsofglobalhealth.org/articles/1176
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author Jessica E. Laine
Rebecca C. Fry
author_facet Jessica E. Laine
Rebecca C. Fry
author_sort Jessica E. Laine
collection DOAJ
description Background: <a title="Learn more about Prenatal Exposure" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/prenatal-exposure">Prenatal exposure</a> to inorganic arsenic (iAs) is associated with dysregulated fetal gene and protein expression. Potential biological mechanisms that underlie these changes include, but are not limited to, changes to the epigenome. Objective: The aim of the present study was to identify whether the expression of key genes, proteins, or both and their associated biological pathways are perturbed by compiling datasets from studies on prenatal arsenic exposure. Methods: We compiled datasets from 12 studies that analyzed the relationship between prenatal iAs exposure and changes to the fetal epigenome (5-methyl cytosine), <a title="Learn more about Transcriptome" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/transcriptome">transcriptome</a> (mRNA expression), and/or <a title="Learn more about Proteome" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/proteome">proteome</a> (protein expression). Findings: Across the 12 studies, a set of 845 unique genes was identified and found to enrich for their role in biological pathways, including the <a title="Learn more about Peroxisome Proliferator-activated Receptor" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/peroxisome-proliferator-activated-receptor">peroxisome proliferator-activated receptor</a>, nuclear factor of kappa light polypeptide gene enhancer in <a title="Learn more about B Cell" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/b-cell">B-cells</a> inhibitor, and the <a title="Learn more about Glucocorticoid Receptor" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/glucocorticoid-receptor">glucocorticoid receptor</a>. <a title="Learn more about Tumor Necrosis Factor" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/tumor-necrosis-factor">Tumor necrosis factor</a> was identified as a putative cellular regulator underlying most (n = 277) of the identified iAs-associated gene or protein expression changes. Conclusions: The identification of the common set of genes across numerous human cohorts suggests a conserved biological response to prenatal arsenic exposure. The genes/proteins and their associated pathways may be useful in future mechanistic investigations of iAs associated diseases.
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spelling doaj.art-639d6b76b90e4e08996aa9ea273a22d82022-12-21T18:01:51ZengUbiquity PressAnnals of Global Health2214-99962016-06-0182118919610.1016/j.aogh.2016.01.0151086A Systems Toxicology-based Approach Reveals Biological Pathways Dysregulated by Prenatal Arsenic ExposureJessica E. Laine0Rebecca C. Fry1Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NCDepartment of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NCBackground: <a title="Learn more about Prenatal Exposure" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/prenatal-exposure">Prenatal exposure</a> to inorganic arsenic (iAs) is associated with dysregulated fetal gene and protein expression. Potential biological mechanisms that underlie these changes include, but are not limited to, changes to the epigenome. Objective: The aim of the present study was to identify whether the expression of key genes, proteins, or both and their associated biological pathways are perturbed by compiling datasets from studies on prenatal arsenic exposure. Methods: We compiled datasets from 12 studies that analyzed the relationship between prenatal iAs exposure and changes to the fetal epigenome (5-methyl cytosine), <a title="Learn more about Transcriptome" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/transcriptome">transcriptome</a> (mRNA expression), and/or <a title="Learn more about Proteome" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/proteome">proteome</a> (protein expression). Findings: Across the 12 studies, a set of 845 unique genes was identified and found to enrich for their role in biological pathways, including the <a title="Learn more about Peroxisome Proliferator-activated Receptor" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/peroxisome-proliferator-activated-receptor">peroxisome proliferator-activated receptor</a>, nuclear factor of kappa light polypeptide gene enhancer in <a title="Learn more about B Cell" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/b-cell">B-cells</a> inhibitor, and the <a title="Learn more about Glucocorticoid Receptor" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/glucocorticoid-receptor">glucocorticoid receptor</a>. <a title="Learn more about Tumor Necrosis Factor" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/tumor-necrosis-factor">Tumor necrosis factor</a> was identified as a putative cellular regulator underlying most (n = 277) of the identified iAs-associated gene or protein expression changes. Conclusions: The identification of the common set of genes across numerous human cohorts suggests a conserved biological response to prenatal arsenic exposure. The genes/proteins and their associated pathways may be useful in future mechanistic investigations of iAs associated diseases.https://annalsofglobalhealth.org/articles/1176CpG methylationgene expressioninorganic arsenicmicroRNA expressionprotein expression
spellingShingle Jessica E. Laine
Rebecca C. Fry
A Systems Toxicology-based Approach Reveals Biological Pathways Dysregulated by Prenatal Arsenic Exposure
Annals of Global Health
CpG methylation
gene expression
inorganic arsenic
microRNA expression
protein expression
title A Systems Toxicology-based Approach Reveals Biological Pathways Dysregulated by Prenatal Arsenic Exposure
title_full A Systems Toxicology-based Approach Reveals Biological Pathways Dysregulated by Prenatal Arsenic Exposure
title_fullStr A Systems Toxicology-based Approach Reveals Biological Pathways Dysregulated by Prenatal Arsenic Exposure
title_full_unstemmed A Systems Toxicology-based Approach Reveals Biological Pathways Dysregulated by Prenatal Arsenic Exposure
title_short A Systems Toxicology-based Approach Reveals Biological Pathways Dysregulated by Prenatal Arsenic Exposure
title_sort systems toxicology based approach reveals biological pathways dysregulated by prenatal arsenic exposure
topic CpG methylation
gene expression
inorganic arsenic
microRNA expression
protein expression
url https://annalsofglobalhealth.org/articles/1176
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