Adhesion of trophoblast to uterine epithelium as related to the state of trophoblast differentiation: In vitro studies using cell lines

At the initial phase of embryo implantation, the trophoblast must have acqu ired competence for adhesion to the uterine epithelium, a condition whose c ell biological basis is far from understood. In the present study, trophobl ast-type cells (BeWo, JAr, and Jeg-3 choriocarcinoma cell lines) were treat ed with retinoic acid, methotrexate, dibutyryl-cAMP, or phorbol-12-myristat e-13-acetate in order to modulate their ability to adhere to uterine epithe lial cells (RL95-2). In an established model, multicellular spheroids of ch oriocarcinoma cells were transferred onto the surface of monolayer cultures of RL95-2 cells followed by a centrifugal force-based adhesion assay. In c ontrols, about 45% of BeWo and JAr cell spheroids and 75% of Jeg-3 spheroid s adhered to uterine monolayers within 30 min. Pretreatment of spheroids wi th either of the agents stimulated differentiation as indicated by the rate of chorionic gonadotropin secretion, but consistently reduced the adhesion to the endometrial monolayer in all three choriocarcinoma cell lines. Whil e previous investigations had shown that invasiveness of trophoblast cells (into extracellular matrix) does not seem to be linked to the differentiati on program in a simple manner, the present data suggest that such an (inver se) link may indeed exist with respect to the ability to initiate an adhesi ve interaction with the uterine epithelium. These observations support the view that epithelial cell interactions as typical for the initial phase of embryo implantation are regulated in a way that is clearly different from c ell-matrix interactions governing later phases of trophoblast invasion into the endometrial stroma, Mol. Reprod. Dev. 57:135-145, 2000. (C) 2000 Wiley -Liss, Inc.