Placental Transfer of Conjugated Bisphenol A and Subsequent Reactivation in the Rat Fetus
http://ehp03.niehs.nih.gov/article/info%3Adoi%2F10.1289%2Fehp.0901575
Background: Bisphenol A (BPA), a famous endocrine disruptor, is highly glucuronidated in the liver and the resultant BPA-glucuronide (BPA-GA) is excreted, primarily into bile. However, in rodents, prenatal exposure to low doses of BPA can adversely affect the fetus, despite the efficient drug metabolizing systems of the dams. The transport mechanisms of BPA from mother to fetus are also unknown.
http://ehp03.niehs.nih.gov/article/info%3Adoi%2F10.1289%2Fehp.0901575
Background: Bisphenol A (BPA), a famous endocrine disruptor, is highly glucuronidated in the liver and the resultant BPA-glucuronide (BPA-GA) is excreted, primarily into bile. However, in rodents, prenatal exposure to low doses of BPA can adversely affect the fetus, despite the efficient drug metabolizing systems of the dams. The transport mechanisms of BPA from mother to fetus are also unknown.
Objectives: We hypothesized that BPA-GA, which is an inactive metabolite, is passed through the placenta to the fetus, where it affects the fetus after reactivation. We thus investigated placental transfer of BPA-GA and reactivation to BPA in the fetus.
Methods: Uterine perfusion with BPA-GA was performed using pregnant rats. The expression and localization of the placental transporters for drug metabolites were examined by RT-PCR and immunohistochemistry. The deconjugation of BPA-GA in the fetus was also investigated. UDP-glucuronosyltransferase (UGT) activity toward BPA and the expression of UGT isoforms were examined in fetal liver.
Results: BPA-GA and deconjugated BPA were detected in the fetus and amniotic fluid after perfusion. In the trophoblast cells, organic anion-transporting polypeptide 4a1 (Oatp4a1) were localized on the apical membrane and multidrug resistance-associated protein 1 (Mrp1) on the basolateral membrane. Deconjugation of BPA-GA was observed in the fetus. Furthermore, the expression of UGT 2B1, which metabolizes BPA, was quite low in the fetus.
Conclusions: These results demonstrate that BPA-GA is transferred into the fetus and deconjugated in the fetus due to its vulnerable drug metabolizing system.
