Receptor-Mediated Endocytosis across Human Placenta: Emphasis on Megalin

Receptor-mediated endocytosis plays an important role in the maternal-fetal transport of various nutrients and drugs across human placenta. Megalin, a 600 kDa endocytic receptor, is expressed in placental syncytiotrophoblasts and is thought to contribute to the transport functions of the placenta. However, the molecular mechanisms involved in megalin-mediated transplacental transport of most substrates have not yet been characterized. Megalin is most extensively expressed on the apical surface of renal proximal tubular epithelial cells, where it is involved in the reabsorption of proteins, vitamins, and polybasic drugs including aminoglycoside (AG) antibiotics. It has been suggested that megalin-mediated endocytosis is primarily responsible for accumulation of aminoglycosides (AGs) in the renal proximal tubule, which results in direct cellular injury and death. The role of megalin in the renal uptake and accumulation of aminoglycosides has therefore received much attention. It is not known, however, whether megalin is involved in the maternal-fetal transport of AGs and other commonly used polybasic drugs. Studies designed to characterize the role of megalin in transplacental transport and to understand the molecular mechanisms involved in megalin-mediated endocytosis across human placenta are therefore needed.