Placental transfer of conjugated bisphenol A and subsequent reactivation in the rat fetus

Environ Health Perspect. 2010 Sep;118(9):1196-203. doi: 10.1289/ehp.0901575. Epub 2010 Apr 9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amniotic Fluid / metabolism
  • Animals
  • Benzhydryl Compounds
  • Chromatography, High Pressure Liquid
  • Female
  • Fetus / metabolism*
  • Glucuronides / metabolism*
  • Immunohistochemistry
  • Mass Spectrometry
  • Phenols / metabolism*
  • Placenta / metabolism
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Benzhydryl Compounds
  • Glucuronides
  • Phenols
  • bisphenol A glucuronide