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Review

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

1
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695, USA
2
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Miguel Machado Santos
Toxics 2021, 9(4), 77; https://doi.org/10.3390/toxics9040077
Received: 3 March 2021 / Revised: 27 March 2021 / Accepted: 2 April 2021 / Published: 6 April 2021
(This article belongs to the Special Issue Advanced Zebrafish Model for Environmental Health Sciences Research)
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. View Full-Text
Keywords: endocrine-disrupting chemical (EDC); gene-environment interaction (GxE); differential susceptibility endocrine-disrupting chemical (EDC); gene-environment interaction (GxE); differential susceptibility
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MDPI and ACS Style

Wallis, D.J.; Truong, L.; La Du, J.; Tanguay, R.L.; Reif, D.M. Uncovering Evidence for Endocrine-Disrupting Chemicals That Elicit Differential Susceptibility through Gene-Environment Interactions. Toxics 2021, 9, 77. https://doi.org/10.3390/toxics9040077

AMA Style

Wallis DJ, Truong L, La Du J, Tanguay RL, Reif DM. Uncovering Evidence for Endocrine-Disrupting Chemicals That Elicit Differential Susceptibility through Gene-Environment Interactions. Toxics. 2021; 9(4):77. https://doi.org/10.3390/toxics9040077

Chicago/Turabian Style

Wallis, Dylan J., Lisa Truong, Jane La Du, Robyn L. Tanguay, and David M. Reif. 2021. "Uncovering Evidence for Endocrine-Disrupting Chemicals That Elicit Differential Susceptibility through Gene-Environment Interactions" Toxics 9, no. 4: 77. https://doi.org/10.3390/toxics9040077

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