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Uncovering Evidence for Endocrine-Disrupting Chemicals That Elicit Differential Susceptibility through Gene-Environment Interactions

Exposure to endocrine-disrupting chemicals (EDCs) is linked to myriad disorders, characterized by the disruption of the complex endocrine signaling pathways that govern development, physiology, and even behavior across the entire body. The mechanisms of endocrine disruption involve a complex system...

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Autores principales: Wallis, Dylan J., Truong, Lisa, La Du, Jane, Tanguay, Robyn L., Reif, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067468/
https://www.ncbi.nlm.nih.gov/pubmed/33917455
http://dx.doi.org/10.3390/toxics9040077
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author Wallis, Dylan J.
Truong, Lisa
La Du, Jane
Tanguay, Robyn L.
Reif, David M.
author_facet Wallis, Dylan J.
Truong, Lisa
La Du, Jane
Tanguay, Robyn L.
Reif, David M.
author_sort Wallis, Dylan J.
collection PubMed
description Exposure to endocrine-disrupting chemicals (EDCs) is linked to myriad disorders, characterized by the disruption of the complex endocrine signaling pathways that govern development, physiology, and even behavior across the entire body. The mechanisms of endocrine disruption involve a complex system of pathways that communicate across the body to stimulate specific receptors that bind DNA and regulate the expression of a suite of genes. These mechanisms, including gene regulation, DNA binding, and protein binding, can be tied to differences in individual susceptibility across a genetically diverse population. In this review, we posit that EDCs causing such differential responses may be identified by looking for a signal of population variability after exposure. We begin by summarizing how the biology of EDCs has implications for genetically diverse populations. We then describe how gene-environment interactions (GxE) across the complex pathways of endocrine signaling could lead to differences in susceptibility. We survey examples in the literature of individual susceptibility differences to EDCs, pointing to a need for research in this area, especially regarding the exceedingly complex thyroid pathway. Following a discussion of experimental designs to better identify and study GxE across EDCs, we present a case study of a high-throughput screening signal of putative GxE within known endocrine disruptors. We conclude with a call for further, deeper analysis of the EDCs, particularly the thyroid disruptors, to identify if these chemicals participate in GxE leading to differences in susceptibility.
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spelling pubmed-80674682021-04-25 Uncovering Evidence for Endocrine-Disrupting Chemicals That Elicit Differential Susceptibility through Gene-Environment Interactions Wallis, Dylan J. Truong, Lisa La Du, Jane Tanguay, Robyn L. Reif, David M. Toxics Review Exposure to endocrine-disrupting chemicals (EDCs) is linked to myriad disorders, characterized by the disruption of the complex endocrine signaling pathways that govern development, physiology, and even behavior across the entire body. The mechanisms of endocrine disruption involve a complex system of pathways that communicate across the body to stimulate specific receptors that bind DNA and regulate the expression of a suite of genes. These mechanisms, including gene regulation, DNA binding, and protein binding, can be tied to differences in individual susceptibility across a genetically diverse population. In this review, we posit that EDCs causing such differential responses may be identified by looking for a signal of population variability after exposure. We begin by summarizing how the biology of EDCs has implications for genetically diverse populations. We then describe how gene-environment interactions (GxE) across the complex pathways of endocrine signaling could lead to differences in susceptibility. We survey examples in the literature of individual susceptibility differences to EDCs, pointing to a need for research in this area, especially regarding the exceedingly complex thyroid pathway. Following a discussion of experimental designs to better identify and study GxE across EDCs, we present a case study of a high-throughput screening signal of putative GxE within known endocrine disruptors. We conclude with a call for further, deeper analysis of the EDCs, particularly the thyroid disruptors, to identify if these chemicals participate in GxE leading to differences in susceptibility. MDPI 2021-04-06 /pmc/articles/PMC8067468/ /pubmed/33917455 http://dx.doi.org/10.3390/toxics9040077 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Wallis, Dylan J.
Truong, Lisa
La Du, Jane
Tanguay, Robyn L.
Reif, David M.
Uncovering Evidence for Endocrine-Disrupting Chemicals That Elicit Differential Susceptibility through Gene-Environment Interactions
title Uncovering Evidence for Endocrine-Disrupting Chemicals That Elicit Differential Susceptibility through Gene-Environment Interactions
title_full Uncovering Evidence for Endocrine-Disrupting Chemicals That Elicit Differential Susceptibility through Gene-Environment Interactions
title_fullStr Uncovering Evidence for Endocrine-Disrupting Chemicals That Elicit Differential Susceptibility through Gene-Environment Interactions
title_full_unstemmed Uncovering Evidence for Endocrine-Disrupting Chemicals That Elicit Differential Susceptibility through Gene-Environment Interactions
title_short Uncovering Evidence for Endocrine-Disrupting Chemicals That Elicit Differential Susceptibility through Gene-Environment Interactions
title_sort uncovering evidence for endocrine-disrupting chemicals that elicit differential susceptibility through gene-environment interactions
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067468/
https://www.ncbi.nlm.nih.gov/pubmed/33917455
http://dx.doi.org/10.3390/toxics9040077
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