Retinoic Acid Inhibits Uterotrophic Activity of Bisphenol A in Adult Ovariectomized Rats

Abstract

Bisphenol A (BPA) is used in the production of polycarbonate and epoxy resins. The weak estrogenic activity of BPA has been confirmed by both in vitro and in vivo assays. Retinal acetate has been reported to inhibit the adverse effects of BPA on male mice reproduction. All-trans-retinoic acid (ATRA) is a potent natural derivative of vitamin A and is reported to inhibit the estrogen-induced proliferation of human breast carcinoma cells. In this study, we investigated the possible inhibitory effects of ATRA on the estrogenic activity of BPA by a standard in vivo uterotrophic assay. Proliferated and apoptotic uterine cells were identified by 5-bromo-2'deoxyuridine (BrdU) incorporation and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. We observed that ATRA supplementation significantly inhibits a BPA-induced uterine weight increase in adult ovariectomized rats. However, there were no significant differences in the increases in the numbers of BrdU-positive cells and TUNEL-positive cells between the BPA and BPA+ATRA groups. These results show that ATRA may have an inhibitory effect on the estrogenic activity of BPA in an in vivo assay.