@article{oai:rakuno.repo.nii.ac.jp:00002370,
 author = {Nishikawa, Miyu and Iwano, Hidetomo and Yanagisawa, Risa and Koike, Nanako and Inoue, Hiroki and Yokota, Hiroshi},
 issue = {9},
 journal = {Environmental Health Perspectives},
 month = {Sep},
 note = {Article, Background : Bisphenol A (BPA), a well-known 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 unknown. Objectives : To test our hypothesis that BPA-GA—an inactive metabolite—is passed through the placenta to the fetus, where it affects the fetus after reactivation, we investigated the placental transfer of BPA-GA and reactivation to BPA in the fetus. Methods : After performing uterine perfusion with BPA-GA in pregnant rats, we examined the expression and localization of the placental transporters for drug metabolites in the perfusate by reverse-transcriptase polymerase chain reaction and immunohistochemistry. We also investigated the deconjugation of BPA-GA in the fetus and examined uridine 5′-diphospho-glucuronosyltransferase (UGT) activity toward BPA and the expression of UGT isoforms in fetal liver. Results : We detected BPA-GA and deconjugated BPA in the fetus and amniotic fluid after perfusion. In the trophoblast cells, organic anion-transporting polypeptide 4a1 (Oatp4a1) was localized on the apical membrane, and multidrug resistance-associated protein 1 (Mrp1) was localized to the basolateral membrane. We observed deconjugation of BPA-GA in the fetus; furthermore, we found the expression of UGT2B1, which metabolizes BPA, to be quite low in the fetus. Conclusions : These results demonstrate that BPA-GA is transferred into the fetus and deconjugated in the fetus because of its vulnerable drug-metabolizing system.},
 pages = {1196--1203},
 title = {Placental transfer of conjugated bisphenol A and subsequent reactivation in the rat fetus},
 volume = {118},
 year = {2010}
}