INTERACTIONS BETWEEN TROPHOBLAST AND UTERINE EPITHELIUM - MONITORING OF ADHESIVE FORCES

At embryo implantation, it is postulated that the initial contact betw een blastocyst and maternal tissues is by adhesion of the trophoblast to the uterine epithelium. This cell-to-cell interaction is thought to be critical for implantation, although the actual adhesive forces hav e never been determined, In the present study, the atomic force micros cope (AFM) was used to study the adhesion between human uterine epithe lial cell lines (HEC-1-A; RL95-2) and human trophoblast-type cells (JA R), Specific interaction forces of these epithelia via their apical ce ll poles were determined on the basis of approach-and-separation cycle s, For this purpose, the AFM tip was functionalized with JAR cells, th en brought to the surface of uterine epithelial monolayers and was kep t in contact for different periods of time (ms, 1, 10, 20, 40 min), Th e approach force curves displayed repulsive interactions for both HEC- 1-A and RL95-2 cells, However, RL95-2 cells (with a smooth surface str ucture and a thin glycocalyx) showed lower values of the repulsive reg ime than HEC-1-A cells (with a rough surface structure and a thick gly cocalyx), After having overcome repulsive interactions, the initial co ntact was followed by adhesive interactions. For contact times of 20 a nd 40 min, RL95-2 cells, but not HEC-1-A cells, showed specific JAR bi nding, i.e. the separation force curves displayed repeated rupture eve nts in the range of 1-3 nN with a distance between 7-15 mu m and, ther eafter, a final rupture event at a distance of up to 45 mu m, These fe atures point to the formation of strong cell-to-cell bonds, Collective ly, these studies provide the first definition of interaction forces b etween the trophoblast and the uterine epithelium, and are consistent with the hypothesis that an RL95-2-like architecture of uterine epithe lial cells, i.e. an non-polarized phenotype, is essential for apical a dhesiveness for the human trophoblast.