The role of the placenta in fetal exposure to xenobiotics: importance of membrane transporters and human models for transfer studies. Drug Metab. Dispos

The placenta is a key organ in fetal growth and development because 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 metab-olism 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 spe-cies are heterogeneous in their morphology and in their expression of membrane transporters and metabolizing proteins. These char-acteristics raise the difficulty of obtaining a good representative model of human placental transfer. To date, different in vitro, in vivo, and ex vivo tools have been used to elucidate transport and metabolism processes in the human placenta. This study recapit-ulates the typical features of human placenta and then presents the placental enzymes of xenobiotic metabolism, ATP-binding cas-sette transporters, solute carrier transporters, and their role in fetal exposure to xenobiotics. The study also compares the char-acteristics of different models of human placenta, in terms of membrane localization of transporters, and the expression of xe-nobiotic metabolism enzymes. The use of these models for toxi-cological studies, in particular xenobiotic transfer, is described, and the advantages and limits of each model are summarized