Expression of urokinase, plasminogen activator inhibitors and urokinase receptor in pregnant rhesus monkey uterus during early placentation

We have investigated plasmin mediated proteolysis associated with trophobla st invasion during early stages of pregnancy in the rhesus monkey. In situ hybridization and immunocytochemical localization were used to define the c ellular and tissue distribution of urokinase plasminogen activator (uPA), p lasminogen activator inhibitor type 1 (PAI-1) and 2 (PAI-2) and urokinase r eceptor in early monkey placenta and uterus. Our results indicate: (1) uPA is expressed in proliferating and invasive cytotrophoblast located in chori onic villi as well as in extravillous trophoblast associated with uterine a rterioles, This raises the possibility that urokinase may play an important role in trophoblast invasion. (2) PAI-1 mRNA is specifically localized in two areas where invasive trophoblast cells encounter maternal tissue direct ly. The extravillous cytotrophoblast cells at the maternofetal junction exp ress PAI-1 mRNA. The invasive endovascular trophoblast cells within the ute rine arterioles also express PAI-1 mRNA. The location sensitive expression of PAI-1 mRNA at the maternofetal junction may imply a protective function of this protease inhibitor that might be induced through interaction with d ecidual cells. (3) Urokinase receptor antigen has also been found at the ma ternofetal junction and in endovascular trophoblast cells of the invaded ma ternal blood vessel. (4) PAI-2 immunoreactivity is found in association wit h cytotrophoblast cells in anchoring choronic villi suggesting ifs associat ion with early placentation. In conclusion, we propose that the plasmin/pla sminogen activator system may not only regulate extracellular matrix degrad ation, bur also modify migration and invasive behaviour of extravillous tro phoblast cells, during early placentation. (C) 2000 Harcourt Publishers Ltd .