Epithelial-mesenchymal transition during trophoblast differentiation.

Embryo implantation in higher primates is mediated by trophoblast: in the earliest phases by syncytiotrophoblast, then by both cytotrophoblast and syncytiotrophoblast. In the course of placentation three main trophoblast populations can be identified: cytotrophoblast stem cells and two differentiated derivative cell types: the syncytiotrophoblast and the extravillous cytotrophoblast. The syncytiotrophoblast remains mainly epithelial while the extravillous cytotrophoblast undergoes an epithelial-mesenchymal transition (EMT), initially forming multilayered cell columns and then, in human, infiltrating deeply the maternal decidual stroma and blood vessels. Finally, some infiltrating cells differentiate further to become giant cells of the placental bed and myometrium. During the course of these events the extravillous cytotrophoblast acquires a distinct phenotype, losing some typical epithelial components (e.g. E-cadherin, integrin alpha 6 beta 4), but retaining others (e.g. cytokeratins). The signals that trigger this EMT are not well understood but its realisation is of critical importance for pregnancy success.