Chapter 67 - The Significance of ABC Transporters in Human Placenta for the Exposure of Fetus to Xenobiotics

Abstract

Human placenta expresses a variety of ATP-binding cassette (ABC) transporters many of which have been shown to be not only protective against fetal exposure but also important for physiological functions such as nutrient transport. ABC transporters are expressed in all membranes of the fetomaternal barrier of human placenta. Especially important from toxicology point of view are ABCB1/MDR (multidrug resistance)1/P-gp (P-glycoprotein) and ABCG2/BCRP (breast cancer resistance protein), which are expressed on the brush border membrane of syncytiotrophoblast facing maternal blood. As efflux transporters, they transport toxic compounds away from the fetal compartment to the maternal circulation. In animal and placental perfusion studies, it has been shown that inhibition of these transporters increases fetal exposure and fetotoxicity. Several genetic variations in ABC transporter genes have been found but only some of them have been studied on the functional significance to fetal exposure. Because placenta varies more than any other organ between species, human models are important for placental transporter studies. Possibilities include human choriocarcinoma cell lines, isolated primary trophoblastic cells, placental villus cultures, and human placental perfusion, which retains the physiological conditions best of these models. Naturally, in vivo studies would be valuable, but are possible only in the case of clinically necessary drugs and accidental and environmental exposure in pregnant women.