TitleUncovering Evidence for Endocrine-Disrupting Chemicals That Elicit Differential Susceptibility through Gene-Environment Interactions.
Publication TypeJournal Article
Year of Publication2021
AuthorsWallis, DJ, Truong, L, La Du, JK, Tanguay, RL, Reif, DM
Date Published2021 Apr 06

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.

Alternate JournalToxics
PubMed ID33917455
PubMed Central IDPMC8067468
Grant ListP30 ES025128 / ES / NIEHS NIH HHS / United States
ES030007 / NH / NIH HHS / United States
R01 CA161608 / CA / NCI NIH HHS / United States
P30 ES030287 / ES / NIEHS NIH HHS / United States
P42 ES031009 / ES / NIEHS NIH HHS / United States
R56 ES030007 / ES / NIEHS NIH HHS / United States
P42 ES016465 / ES / NIEHS NIH HHS / United States