Expression of members of the multidrug resistance protein family in human term placenta

The placenta serves, in part, as a barrier to exclude noxious substances fr om the fetus. In humans, a single-layered syncytium of polarized trophoblas t cells and the fetal capillary endothelium separate the maternal and fetal circulations. P-glycoprotein is present in the syncytiotrophoblast through out gestation, consistent with a protective role that limits exposure of th e fetus to hydrophobic and cationic xenobiotics. We have examined whether m embers of the multidrug resistance protein (MRP) family are expressed in te rm placenta. After screening a placenta cDNA library, partial clones of MRP 1, MRP2, and MRP3 were identified. Immunofluorescence and immunoblotting st udies demonstrated that MRP2 was localized to the apical syncytiotrophoblas t membrane. MRP1 and MRP3 were predominantly expressed in blood vessel endo thelia with some evidence for expression in the apical syncytiotrophoblast. ATP-dependent transport of the anionic substrates dinitrophenyl-glutathion e and estradiol-17-beta-glucuronide was also demonstrated in apical syncyti otrophoblast membranes. Given the cellular distribution of these transporte rs, we hypothesize that MRP isoforms serve to protect fetal blood from entr y of organic anions and to promote the excretion of glutathione/glucuronide metabolites in the maternal circulation.