Analysis of the estrogenic activity of bisphenol A in an adult ovarictomized mouse model and its potential synergism with estradiol

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Description: The estrogen receptor (ER) is a nuclear hormone receptor that mediates effects on multiple tissues in the body. Bisphenol A (BPA) is an endocrine disrupting compound (EDC) that is capable of binding with the ER and modulating its activity. BPA is used in the manufacture of plastics and resins, many of which are used for food storage. BPA has been found to leach out of these materials and into foodstuffs. This study seeks to broaden our current understanding of the effects of BPA on estrogen responsive tissues. BPA was found to have an inhibitory effect on uterine wet weight in an adult female ovariectomized mouse model when administered via i.p. injection at a dose of 0.5 mg/kg/day for seven days (7.50 mg for BPA treated compared to 18.33 mg for control; p < 0.05). Neither this dose nor higher doses (5 and 50 mg/kg/day for seven days) produced a significant effect on endometrial volume, luminal epithelial height, terminal end bud density in the mammary gland, expression of C3 mRNA in the uterus, or expression of INDO mRNA in the mammary gland. Synergism between BPA and E2 was noted in the same mouse model on luminal epithelial height and terminal end bud density when 50 mg/kg/day BPA was administered orally in conjunction with 4 μg/kg/day E2 administered via i.p. injection for a period of 28 days (luminal epithelial height: 0.028 mm in the High E2/vehicle group compared to 0.038 in the High E2/BPA group, p<0.01; terminal end bud density: 11% for High E2/vehicle compared to 23% for High E2/BPA group, p<0.05). No effect was noted of BPA administered in the absence of E2. These data, together with previous research performed in our lab points to the ability of BPA to enhance the effect of E2 in a synergistic fashion in an adult female mouse. This result warrants further investigation into the effects of BPA on adult populations so as to extrapolate the effect that exposure to this EDC may be having on human populations.
Language: English
Format: Degree Work