Effects of the xenoestrogen bisphenol A on expression of vascular endothelial growth factor (VEGF) in the rat

Bisphenol-A (BPA) is used to produce polymers for production of polycarbona te and epoxy resins that are used in food containers and dental appliances. BPA binds to estrogen receptors and induces estrogenic activity in a numbe r of biological systems. We recently reported that although Fisher 344 (F34 4) and Sprague-Dawley (S-D) rat strains exhibit different sensitivities to BPA at the level of vaginal epithelial cell proliferation, there was no dif ference in immediate early proto-oncogene expression between the two animal strains. In the present study we investigated the effects of BPA on expres sion of another estrogen-target gene, vascular endothelial growth factor (V EGF), in the uterus, vagina, and pituitary of F344 and S-D rats. Adult rats were ovariectomized and treated with BPA by intraperitoneal injection at c oncentrations of 0.02 to 150 mg/kg body wt. Expression of VEGF was monitore d by RNase protection assay at 2 hr after treatment. There was a significan t effect of dose of BPA on the type of VEGF isoform expressed in the uterus , vagina, and pituitary, BPA induced greater (P < 0.01) levels of VEGF(164) and VEGF(120+188) than VEGF(110) levels. The lowest BPA dose that had a si gnificant (P < 0.05) effect on VEGF expression compared with vehicle treatm ent was 37.5 mg/kg body wt.; dose-response curves did not differ between st rains. This is the first report that the primary response of the uterus, va gina, and pituitary to BPA includes rapid induction of VEGF expression. Due to the capacity of VEGF to engage pleiotropic signaling pathways in other cellular systems, we suggest that modulation of VEFG may play a role in est ablishing the response of estrogen-target organs to estrogenic xenobiotics.