The significance of ABC transporters in human placenta for the exposure of the fetus to xenobiotics

This chapter describes the significance of ABC transporters in human placenta for the exposure of the fetus to xenobiotics. Many xenobiotics go through the placenta very easily by passive diffusion. Passive diffusion is the most common mechanism of transfer and depends on the chemical characteristics of compounds, such as molecular weight, lipid solubility, binding to proteins and the degree of ionization. The first part of this chapter details the structure, function and polymorphisms of human efflux ABC transporters. The experimental models used to study placental transfer processes in vitro include placental perfusion, cultured placental tissue explants or isolated villous trees, primary cell cultures, immortalized or cancer cell lines, placental membrane vesicles and cloned transporters. These studies give an idea how the compounds reach the fetus and increase understanding of the significance of transplacental transport in vivo. Because animal studies, especially transporter knockout mice, have given valuable data about the significance of the role of transporters in fetal exposure and fetotoxicity, some of those data are also included. Since ABC transporters take part in important functions in body, it is no wonder that genetic polymorphisms of the transporters are known or suspected to be linked to diseases of many organs. Studies on gene knockout transgenic mice have clearly shown the importance of placental transporters in the protection against toxic insult to the fetus.