EXPRESSION AND FUNCTION OF THE UROKINASE-TYPE PLASMINOGEN-ACTIVATOR DURING MOUSE HEMOCHORIAL PLACENTAL DEVELOPMENT

Mouse midlate placental development involves extensive tissue remodeli ng and cell invasion, processes which could be mediated by extracellul ar proteolytic enzymes, We have performed in situ expression analysis of urokinase type plasminogen activator (uPA), as well as functionally related molecules (uPA receptor, low density lipoprotein receptor-rel ated protein, plasminogen activator inhibitor type-1) in day 10.5 to 1 8.5 post coitum (p.c.) murine placentas, In situ hybridization demonst rated the presence of uPA transcripts in the invasive trophoblast cell s, in particular in glycogen-rich trophoblasts, a cell population that between embryonic days 12.5 and 15.5 infiltrates the maternal decidua l tissue. In addition, we observed high uPA expression in the cells of uterine epithelium, Enzymatically active uPA was detected in both sit es of uPA mRNA expression by in situ zymography Expression and activit y data suggest a role for this protease in the processes of cell invas ion and uterine epithelial remodeling. Only low levels of uPA receptor (uPAR) transcripts were found in trophoblasts and decidual tissue at days 10.5 and 11.5 p.c. At the same stages, a prominent expression of plasminogen activator inhibitor type-1 (PAI-1) by spongiotrophoblasts and giant trophoblasts, as well. as of LDL receptor-related protein (L RP) by spongiotrophoblasts and decidual cells could be detected, sugge sting a role in regulating extracellular proteolysis in the area of fe tomaternal interface. Analysis of uPA null placentas showed the presen ce of decidual extravascular fibrin deposits, which were not detected in wild type placentas, At the same time, the extent of infiltration o f trophoblast cells in maternal decidual tissue, evaluated by anti-cyt okeratin immunostaining, was similar in wild type and uPA null placent as, Our studies show that in murine hemochorial placentation, uPA has an essential role in the maintenance of the fibrinogenic/fibrinolytic balance in the decidua, The function of uPA in trophoblast invasion ap pears not to be indispensable, and its absence can be overcome by redu ndant or compensatory mechanisms, Dev, Dyn. 1998;213:2738. (C) 1998 Wi ley-Liss, Inc.