Implantation: a Cell Biological Paradox

Implantation initiation in eutherian mammals requires, at least in invasive types of implantation, that 1) the trophoblast or subpopulations of it have reached a state of "invasiveness" and, synchronously, 2) the endometrium has reached a state of "receptivity" ("implantation window"). The cell biological basis of "receptivity" as well as of "invasiveness" has long remained unknown, but recently it appears that the application of modern concepts of cell and developmental biology is opening new views of it, concentrating on cell adhesion and cell polarity phenomena. Implantation initiation requires that the trophoblast attaches via its apical plasma membrane to the apical plasma membrane of the uterine epithelium. Since apical plasma membranes of epithelia are normally non-adhesive, this represents a cell biological paradox. In development, cells can express two major phenotypes and switch between these: 1) the mesenchymal/fibroblastoid phenotype that is compatible with cells moving individually; 2) the epithelioid phenotype which is characterized by cells expressing apico-basal polarity and a strong association with neighbouring cells via various junctions, so that they can migrate as sheets but not as individual cells. Application of this concept to embryo implantation would seem to lead to the hypothesis that the trophoblast of blastocysts has to give up part of its typical epithelial organization when becoming invasive; it must express cell-cell adhesion molecules or matrix receptors non-typically at its apical plasma membrane, change the spectrum of expressed adhesion molecules, and alter its motility apparatus. This applies in a somewhat similar way to the uterine epithelium at "receptivity". Interestingly, recent data show that a substantial number of differentiation parameters of these cells change in addition. It appears that part of the epithelial differentiation program is down-regulated at this phase. This also suggests interesting new aspects of the basis of steroid hormone action at the endometrium, as well as of trophoblast invasiveness, possibly involving switches in the activity of regulatory "master" genes as are also involved in decision making during development.