description) Bisphenol A is a widely distributed compound that is found in a variety of consumer products, including polycarbonate water jugs and pipes, the lacquer inner coating of cans, and restorative dental materials. It is released from these products during heating or ordinary wear. Bisphenol A has two hydroxyl phenolic rings capable of mimicking the A-ring of estradiol and of acting as a classical estrogen by competitively binding to the estrogen receptor, albeit only at a concentration 1,000-10,000 times that of estradiol. However, the mechanisms whereby this and other estrogenic compounds perturb developmental processes are largely unknown. This proposal will test the overall hypothesis that bisphenol A produces irreversible alterations in the development and physiological function of estrogen responsive tissues in the female (specifically the oviduct and uterus), resulting in suboptimal fertility.
Specific Aim 1 is a) to determine the uterotropic dose of bisphenol A in vivo by measuring wet weight, to define doses for evaluation of fetal development; b) to determine the availability of bisphenol A in the fetus (based on binding to alpha fetoprotein); and c) to determine the distribution of bisphenol A in the fetal genital tract following in utero or neonatal exposure using autoradiography, HPLC, or mass spectrometry.
Specific Aim 2 is to determine the effects of prenatal exposure to bisphenol A on the structure and function of the uterus and oviduct. Pregnant mice will be exposed to varying concentrations of bisphenol A at the time of genital tract organogenesis (days 9-16 of gestation), and the uterus and oviduct of female offspring will be analyzed using morphological, biochemical and molecular biological techniques.
Specific Aim 3 is to determine the effects of neonatal exposure to bisphenol A on the structure and function of the uterus and oviduct, and to determine whether the effects observed by direct exposure of newborns differs from those as a result of indirect, transplacental exposure of fetuses. Varying concentrations of bisphenol A will be administered to neonatal mice at days 1-5 of age and the uterus and oviduct analyzed using morphological, biochemical and molecular biological techniques. The information obtained from these studies will advance our understanding of the fundamental mechanisms by which xenoestrogens affect female genital tract development and fertility.
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