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Applying EcoToxChips to Identify Potential Gene Expression Markers of Exposure to Glucocorticoid Receptor Agonists
Citation:
Collins, J., J. Cavallin, A. Cole, K. Jensen, M. Kahl, K. Santana Rodriguez, A. Kittelson, AND Dan Villeneuve. Applying EcoToxChips to Identify Potential Gene Expression Markers of Exposure to Glucocorticoid Receptor Agonists. SETAC North America, Pittsburgh, PA, November 13 - 17, 2022. https://doi.org/10.23645/epacomptox.21424434
Impact/Purpose:
Poster presented to SETAC North America meeting Nov 2022. Glucocorticoid receptor (GR) mediated biological activity has been detected in surface waters. However, the causative agents and their relative potency and bioavailability has not been identified. This research identified gene expression changes that can serve as biological markers of exposure to bioavailable GR agonists. Through additional research, it may be possible to identify quantitative response thresholds that may indicate the potential for adverse effects in exposed organisms. Results of this product can improve site specific risk assessments for complex mixtures exhibiting GR-mediated bioactivity which states, tribes, and EPA regions may encounter.
Description:
Glucocorticoid-mediated bioactivity has been detected in North American surface waters. However, the bioavailability and in vivo potency of glucocorticoid receptor (GR) agonists in environmental mixtures remains undefined. To better understand the sensitivity of in vivo, hepatic, gene expression responses to GR agonist exposures, adult male fathead minnows were exposed for 96 h to one of three concentrations of dexamethasone (40 ng/L; 0.40 mg/L; 4.0 mg/L) or to beclomethasone dipropionate (BDP; 130 µg/L). Among several genes with GR-dependent expression in mammals, expression of only one, sgk1, was impacted at a field-relevant concentration of dexamethasone equivalents (i.e., 40 ng/L). The 384 well fathead minnow EcoToxChip v. 1.0 was then employed to identify other potential transcriptomic markers of GR-agonist exposure. Among 375 genes evaluated, six genes were differentially expressed across more than one treatment and identified as biomarker candidates for GR-agonism. The up-regulated genes were acsl5, scd, odc1, and gadd45ga, while the down-regulated genes were slc27a6 and dgat2. The aforementioned genes were identified as they were all found to be sensitive at an environmentally relevant concentration of dexamethasone (40ng/L) and responded in the same direction across all treatments of dexamethasone and BDP. Furthermore, the magnitude of induction and/or down-regulation following dexamethasone was dose-dependent. Results of this study provide additional candidate genes to consider as potential markers of in vivo exposure to GR-agonists in field studies employing caged fish. The contents of this abstract neither constitute, nor necessarily reflect US EPA policy.
URLs/Downloads:
DOI: Applying EcoToxChips to Identify Potential Gene Expression Markers of Exposure to Glucocorticoid Receptor Agonists
COLLINS SETAC POSTER_V5.PDF (PDF, NA pp, 618.931 KB, about PDF)