Date of Award

2017

Embargo Period

8-1-2024

Document Type

Thesis - MUSC Only

Degree Name

Master of Science (MS)

Department

Regenerative Medicine and Cell Biology

College

College of Graduate Studies

First Advisor

Gerard T. Hardiman

Second Advisor

Russell A. Norris

Third Advisor

Bethany J. Wolf

Fourth Advisor

Jeremy L. Barth

Abstract

Exposure to Endocrine Disrupting Chemicals (EDCs) has been connected to the development of a number of adverse outcomes. Of greatest concern are xenoestrogens (XEs), chemicals with the ability to bind to estrogen receptors. The Adverse Outcome Pathway (AOP) framework defines an adverse outcome as the causal result of a series of molecular initiating events (MIEs) and key events (KEs) that change expression. This study aims to utilize transcriptome analysis to identify changes in expression after exposure to environmental levels of XEs, and to exploit systems analysis to determine if these changes to the transcriptome could serve as MIEs. In this study, we performed systems analysis on transcriptome data from primary human cells and zebrafish livers exposed to different xenoestrogens, and examined whether these exposures altered their transcriptomic profiles compared to those cells or organisms not exposed to any EDCs. Our analysis of in vitro, primary human cells demonstrated that exposure to environmental levels of xenoestrogens as low as 0.1 nM resulted in differential expression across three different cell types. Systems analysis of this data demonstrated that these changes were potentially associated with the development of cancer, obesity, and inflammation. Both microarray and RNA-Seq analyses of livers extracted from in vivo model organisms supported these findings, showing that exposure to xenoestrogens was associated with differential expression of genes associated with the development of cancer, steatosis, and inflammation in the liver. Based on the AOP framework, these changes in regulation may serve as MIEs or KEs, though further research will be needed to confirm their connection. Taken together, our results support those of previous studies, namely, that exposure to xenoestrogens potentially results in the development of adverse health outcomes later in life.

Rights

All rights reserved. Copyright is held by the author.

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