Grantee Research Project Results
Investigating the Mechanism of Action and Estrogenic Effects of Bisphenol-A, an Endocrine Disruptor, in the Red-eared Slider Turtle (Trachemys scripta) Model SystemEPA Grant Number: FP917127
Title: Investigating the Mechanism of Action and Estrogenic Effects of Bisphenol-A, an Endocrine Disruptor, in the Red-eared Slider Turtle (Trachemys scripta) Model System
Investigators: Clairardin, Sandrine Georgette
Institution: Illinois State University
EPA Project Officer: Cobbs-Green, Gladys M.
Project Period: September 1, 2010 through August 31, 2012
Project Amount: $74,000
RFA: STAR Graduate Fellowships (2010)
Research Category: Fellowship - Pesticides and Toxic Substances , Academic Fellowships
The overall objective of this project is to understand the mechanism(s) through which Bisphenol-A (BPA) exerts its estrogenic effects with the goal of applying this information to studies of other endocrine disrupting compounds (EDCs). The proposed series of projects outlined in this proposal will test the hypothesis that BPA exerts its estrogenic effects by inhibiting the natural metabolism of estradiol (E2, an estrogen) during development, leading to an increase in available estradiol. This will be done by addressing three main questions: (1) How does BPA affect steroid levels (specifically E2 metabolism)? (2) How does an organism metabolize BPA? (3) How does BPA affect gene expression related to E2 and BPA metabolism?
Many man-made chemicals are released into the environment everyday. Some of these chemicals, called endocrine disrupting compounds (EDCs), can affect the functioning of an organism’s endocrine system and have been shown to have a wide range of negative effects; however, little is understood about how these chemicals produce their effects. This project will test the effects of Bisphenol-A (BPA), an EDC commonly found in plastics, on steroid regulation during development as a possible mechanism.Approach:
The questions will be addressed using the red-eared slider turtle Trachemys scripta as a model system. This system was chosen because a great deal is already known about steroid levels throughout development and the sex of individuals can be experimentally controlled due to their temperature-dependent sex determination (an important characteristic when studying feminizing effects). T. scripta eggs and hatchlings will be treated with BPA in order to gather data concerning levels of steroids (focusing on E2), BPA, and their metabolites, the enzymes responsible for metabolizing E2 and BPA (sulfotransferases, SULT and glucuronyltransferases, UGT for the purposes of this study), and the expression of genes relating to the metabolizing enzymes. This approach combines both in vitro and in vivo studies that will identify which component is ultimately responsible for producing estrogenic effects in the living organism.Expected Results:
These data will show how BPA affects E2 metabolism during a point in development known for steroid sensitivity in this species. In BPA-treated eggs, it is expected that E2 levels will increase in the embryo resulting from the inhibition of SULT activity rather than decreased SULT gene expression. This would indicate that BPA, and other EDCs, may elicit estrogenic effects by increasing available estrogen through SULT inhibition.
Potential to Further Environmental/Human Health Protection:
While substantial advances have been made in determining the impacts of EDCs, most research has focused on understanding the endpoint effects—largely feminizing/estrogenic—of these chemicals in various organisms. Few studies, however, have been done to unravel the mechanisms of action for these compounds. By understanding the mechanisms by which these compounds exert their effects, instead of simply describing the endpoint effects, chemical companies can utilize these ideas during product development, manufacturers can choose safer chemicals for production, and governmental agencies can set more responsible standards and safety guidelines.Supplemental Keywords:
Bisphenol-A, endocrine disruptors, steroid metabolism, sulfotransferase, estradiol, estrogenic effects,