Tissue interactions in the control of trophoblast invasion

On the basis of observations made in an explant model of anchoring villus d evelopment, it is proposed that two discrete types of signal are required t o trigger the entry of cytotrophoblast into the migratory extravillous Line age. The first is mediated by contact of the tip of the first trimester mes enchymal villus with decidual extracellular matrix, in response to which st em villous cytotrophoblast undergoes a proliferative burst and differentiat es into cells of the cytotrophoblast column, anchoring peripheral villi to the uterus. Column stability is dependent on the interaction between extrac ellular fibronectin and integrin alpha 5 beta 1 expressed at the cell surfa ce, both of which are upregulated in this pathway. Subsequently, cells deta ch in large numbers from the periphery of the column and become migratory i nfiltrative 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 anchori ng villus, this mechanism might account for the fact that trophoblast invas ion progresses no deeper than the inner myometrium.