Contributions of drug transporters to blood-placental barrier

Abstract

The placenta is the only organ linking two different individuals, mother and fetus, termed as blood-placental barrier. The functions of the blood-placental barrier are to regulate material transfer between the maternal and fetal circulation. The main functional units are the chorionic villi within which fetal blood is separated by only three or four cell layers (placental membrane) from maternal blood in the surrounding intervillous space. A series of drug transporters such as P-glycoprotein (P-GP), breast cancer resistance protein (BCRP), multidrug resistance-associated proteins (MRP1, MRP2, MRP3, MRP4, and MRP5), organic anion-transporting polypeptides (OATP4A1, OATP1A2, OATP1B3, and OATP3A1), organic anion transporter 4 (OAT4), organic cation transporter 3 (OCT3), organic cation/carnitine transporters (OCTN1 and OCTN2), multidrug and toxin extrusion 1 (MATE1), and equilibrative nucleoside transporters (ENT1 and ENT2) have been demonstrated on the apical membrane of syncytiotrophoblast, some of which also expressed on the basolateral membrane of syncytiotrophoblast or fetal capillary endothelium. These transporters are involved in transport of most drugs in the placenta, in turn, affecting drug distribution in fetus. Moreover, expressions of these transporters in the placenta often vary along with the gestational ages and are also affected by pathophysiological factor. This chapter will mainly illustrate function and expression of these transporters in placentas, their contribution to drug distribution in fetus, and their clinical significance.