Does plasminogen activator inhibitor-1 (PAI-1) control trophoblast invasion? A study of fetal and maternal tissue in intrauterine, tubal and molar pregnancies

Urokinase plasminogen activator, its receptor and the inhibitor PAI-1 are b elieved to central proteolysis and remodelling of maternal tissue during tr ophoblast invasion. This system appears to be strictly regulated in normal intrauterine pregnancies whereas tubal and molar pregnancies seem to be cha racterized by an uncontrolled. excessive placental invasion. This study eva luates subcellular PAI-1 by immunohistochemistry in the villous placenta, i n the basal plate and placental bed, and in the decidual compartments of no rmal, tubal and molar pregnancies. PAI-1 was present in villous syncytiotro phoblasts and co-localized focally with fibrin-type fibrinoid on the surfac e of the chorionic villi. Basal plate and placental bed extravillous inters titial trophoblasts, as well as vascular trophoblasts, were also PAI-1 posi tive. In the decidua parietalis, PAI-1 was observed in the cytoplasm of the non-invaded decidual cells. In the decidua basalis comprising the basal pl ate, PAI-1 was seen to be membrane-associated or confined to the extracerlu lar matrix (ECM) facing the invasive front of anchoring villi. The ECM of d ecidua capsularis and chorion laeve displayed the most pronounced PAI-1 exp ression towards the maternal interface. In contrast, the majority of placen tal bed decidual cells adjacent to the interstitial and vascular trophoblas ts were PAI-1 negative. Only a few stromal cells distant from the implantat ion site were PAI-1 positive in the tubal pregnancies and decidualization w as not present. Likewise, excessive decidual necrosis and fibrinoid deposit ion devoid of PAI-1 was a common finding in complete molar pregnancies. The se results suggest that PAI-1 defines specific extravillous invasive tropho blasts within the maternal decidua. Moreover, maternal cellular lack of PAI -1 in tubal pregnancies and excessive decidual necrosis in molar pregnancie s indicate an uncontrolled placental invasion. The present data indicate th at trophoblast invasion is primarily regulated by signals from decidual cel ls. (C) 2000 Harcourt Publishers Ltd.