Characterization of Endocrine Disrupting Effects of Bisphenol a Or 17Α-Ethinyl Estradiol in Mouse Uterus
Characterization of Endocrine Disrupting Effects of Bisphenol A or 17α-Ethinyl Estradiol in Mouse Uterus A dissertation submitted to the Graduate School of the University of Cincinnati in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Pharmacology and Cell Biophysics of the College of Medicine by Jessica A. Kendziorski BA, DePauw University, 2010 Committee Chair: Scott M. Belcher, PhD ABSTRACT Bisphenol A (BPA) and 17α-ethinyl estradiol (EE) are estrogenic endocrine disrupting chemicals (EDCs) that adversely affect the structure and function of the uterus. Humans are ubiquitously exposed to BPA via consumption of contaminated food and beverage from polycarbonate packaging or food cans. Humans are exposed to EE through the use of oral contraceptives. While human exposure to these EDCs is widespread, little is known how these compounds alter physiological responses that lead to increased incidence of uterine pathology. The purpose of this dissertation was to investigate and characterize uterine pathologies and associated alterations in immune responsiveness and fibrosis. Two mouse strains were used, the CD1 and the C57Bl/6N strains. Exposure during adulthood included mating, parturition, and offspring rearing and mice were exposed for 12-15 weeks. Whole life exposure included placental transfer, as well as direct oral consumption, exposing mice until postnatal day (PND) 90. In order to closely mimic human exposure, mice were orally exposed through diet to known concentrations of control (0 ppm), BPA (0.03, 0.3, 3, 30, or 300 ppm), or EE (0.0001, 0.001, 0.01, 0.1, or 1.3 ppm), which resulted in calculated BPA doses of 0.04, 0.4, 4, 40, and 400 mg/kg/day and EE doses of 0.00002, 0.0002, and 0.001 mg/kg/day.
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