Bisphenol A-induced increase in uterine weight and alterations in uterine morphology in ovariectomized B6G3F1 mice: Role of the estrogen receptor

The ability of the environmental xenoestrogen bisphenol A (BPA) to increase uterine wet weight in the rodent remains controversial, and few studies ha ve previously examined the effects of BPA on uterine morphology. Furthermor e, it is not known whether BPA-induced uterotrophic effects are, similarly to beta-estradiol (E-2), mediated through the estrogen receptor (ER). In th is study, we compared the effects of BPA on uterine wet weight and morpholo gy to those of E-2 in the B6C3F1 ovariectomized mouse. To examine whether t hese effects were mediated through the ER, the antiestrogen ICI 182,780 (IC I) was co-administered with BPA or E-2. We report that subcutaneous adminis tration of BPA at doses between 0.8 and 8 mg/day over 4 days significantly increased mean uterine wet weights above those of vehicle (corn oil)-treate d mice. The uterine weight data suggest that BPA acts as a partial agonist with an EC50 of 0.72 mg/day compared to 19.4 ng/day for E-2. BPA (2 mg/day) and E-2 (40 ng/day) induced a significant increase in luminal epithelial h eight and in the thickness of both the stromal and myometrial layers of the uterus. The effects of 40 ng E-2/day on all endpoints studied were reverse d by 20 pg ICU day. ICI at 200, but not 20 mu g/day, was able to reverse th e BPA (2 mg/day)-induced increase in both uterine wet weight and luminal ep ithelial height. ICI alone at 200 mu g/day stimulated an increase in thickn ess of both the stroma and myometrium and did not reverse the effects of BP A (2 mg/day) on these layers. These results suggest that the BPA-induced in crease in uterine wet weight and in luminal epithelial height in the ovarie ctomized B6C3F1 mouse are mediated by the ER.