Abstract

The placenta is a key organ in fetal growth and development, as it controls maternal-to-fetal exchanges of nutrients and hormones. It also interferes with drug delivery to the fetus, by expressing active membrane transporters and xenobiotic metabolism enzymes. Developing strategies to understand the role of the placenta in drug delivery is a challenge in toxicology. Despite common physiological functions, the placentas of different species are heterogeneous in both their morphology and in their expression of membrane transporters and metabolizing proteins. This raises the difficulty of obtaining a good representative model of human placental transfer. Up to now, different in vitro, in vivo and ex vivo tools have been used to elucidate transport and metabolism processes in the human placenta. After having recapitulated the typical features of human placenta, this review presents the placental enzymes of xenobiotic metabolism, ATP Binding Cassette transporters, Solute Carrier Transporters, and their role in fetus exposure to xenobiotics. It also compares the characteristics of different models of human placenta, in terms of membrane localization of transporters, and the expression of xenobiotic metabolism enzymes. The use of these models for toxicological studies, in particular xenobiotic transfer, is described, and the advantages and limits of each model are summarized.