COLLAGENASE-IV IN HUMAN TROPHOBLAST INVASION AND DIFFERENTIATION

Trophoblast cells are unique with respect to their functions and respo nsibilities. These cells demonstrate three sequential phenotypes, prol iferation and invasion into the endometrium, differentiation to form s yncytia and endocrine secretions. Equipped with these properties place ntal trophoblasts are endowed with a variety of functions, like implan tation of the blastocyst to the endometrium, providing nutrition to th e developing embryo and also transmitting extraordinary array of signa ls for the embryonic development. Experimental evidences and logical e xtrapolation suggest that these functions are precisely controlled by growth factors, cytokines and hormones produced either by the trophobl ast themselves or by the utero-placental unit. Any error in this contr ol mechanism has extremely adverse consequences. The cells also synthe size a large number of enzymes, amongst which collagenase type IV secr etion is involved in digestion of underlying basement membrane necessa ry for the process of invasion. Our results implicate the enzyme in th e functional differentiation of the trophoblast as well. Inhibitors to this enzyme inhibit trophoblast differentiation as monitored by secre tion of hCG and progesterone, the two markers of trophoblastic differe ntiation. In contrast, BeWo cells,a choriocarcinoma cell line which do es not differentiate spontaneously, undergo increased proliferation wh en challenged with EGF. The results indicate the possibility of invasi ve and differentiative phenotypes to be coupled. Exact molecular invol vements in this coupling process are looked into.