Towards an understanding of synthetic glucocorticoid hazards in aquatic systems.

Synthetic glucocorticoids are pharmaceutical compounds that mimic cortisol, the endogenous ligand ubiquitous to vertebrates and bind to the glucocorticoid receptor within the cytoplasm. Here I examine occurrence of these endocrine disrupting contaminants of emerging concern in surface waters and wastewater effluent, identify discrepancies in detection methods, advance an understanding of cross-species susceptibility, and define mechanisms associated with apical outcomes following exposure in aquatic matrices. First, I performed a critical review of existing literature to characterize the global occurrence of synthetic glucocorticoids in freshwater matrices detected by either analytical chemistry methods or bioanalytical surveillance methods. I conducted probabilistic environmental hazard assessments by employing environmental exposure distributions to estimate the probability of exceeding various hazard values. I observed synthetic glucocorticoids to be ubiquitous in freshwater systems, identified discrepancies among methods and geographical regions, and highlighted current data gaps. Next, I compared endpoint sensitivity of various bioanalytical methods employed in surface water surveillance and the potency of synthetic glucocorticoids present in surface waters by employing chemical toxicity distributions. I observed multiple orders of magnitude difference in potency of the various synthetic glucocorticoids, and identified specific assays that were most likely to detect lower levels of glucocorticoid receptor agonism. Next, by employing in silico, in vitro, and in vivo methods, the evolutionary conservation of the glucocorticoid receptor was confirmed, and cross-species susceptibility was demonstrated using the zebrafish (Danio rerio) model in vitro and the fathead minnow (Pimephales promelas) model in vivo. Lastly, I examined the effects of synthetic glucocorticoid exposure on aquatic species by utilizing the adverse outcome pathway framework. I observed the inhibition of fin regeneration following caudal fin damage and exposure to fluticasone propionate (2μg/L) in juvenile fathead minnow and identified mRNA endpoints perturbed by exposure. These phenotypic and subcellular endpoints were then employed to construct an adverse outcome pathway. Additionally, I utilized data collected during in silico and in vitro analysis to define the plausible taxonomic domain of applicability for glucocorticoid receptor agonism. This dissertation integrated diverse new approach methodologies to advance an understanding of the water quality hazards presented by an important class of endocrine disrupting contaminants of emerging concern.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Doctoral

Grantor

Baylor University.

Year dc:date.issued

2024

Author dc:creator

• Cole, Alexander R., 1996-

Advisor dc:contributor.advisor

• Brooks, Bryan W.

• Glucocorticoid.
• Fathead minnow.
• Glucocorticoid receptor.
• Aquatic toxicology.
• Endocrine disruption.

Statement dc:rights

• Baylor University works are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. Contact libraryquestions@baylor.edu for inquiries about permission.

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/2104/13131

OAI identifier oai:identifier

oai:baylor-ir.tdl.org:2104/13131