Tissue interactions in the control of trophoblast invasion

On the basis of observations made in an explant model of anchoring villus development, it is proposed that two discrete types of signal are required to trigger the entry of cytotrophoblast into the migratory extravillous lineage. The first is mediated by contact of the tip of the first trimester mesenchymal villus with decidual extracellular matrix, in response to which stem villous cytotrophoblast undergoes a proliferative burst and differentiates into cells of the cytotrophoblast column, anchoring peripheral villi to the uterus. Column stability is dependent on the interaction between extracellular fibronectin and integrin alpha 5 beta 1 expressed at the cell surface, both of which are upregulated in this pathway. Subsequently, cells detach in large numbers from the periphery of the column and become migratory infiltrative cells. This step is dependent on paracrine signalling from the mesenchymal cells that lie directly beneath the villous basement membrane. As the signal decreases with increasing distance from the placental anchoring villus, this mechanism might account for the fact that trophoblast invasion progresses no deeper than the inner myometrium.