COORDINATED EXPRESSION OF MMP-2 AND ITS PUTATIVE ACTIVATOR, MT1-MMP, IN HUMAN PLACENTATION

The spatial expression of mRNA for matrix metalloproteinase 2 (MMP-2), its putative activator, the membrane-type 1 matrix metalloproteinase (MT1-MMP), and the MMP-2 substrate type IV collagen was investigated i n human placentas of both normal and tubal ectopic pregnancies and in cyclic endometrium using in-situ hybridization. Cytokeratin staining a pplied to adjacent sections was used to identify epithelial and tropho blast cells. In both normal and tubal pregnancies MT1-MMP, MMP-2 and t ype IV collagen mRNA were highly expressed and co-localized in the ext ravillous cytotrophoblasts of anchoring villi, in cytotrophoblasts tha t had penetrated into the placental bed and in cytotrophoblastic cell islands. In addition, the decidual cells of normal pregnancies in some areas co-expressed MT1-MMP and MMP-2 mRNA, with moderate signals for both components. Fibroblast-like stromal cells in tubal pregnancies we re positive for MMP-2 mRNA but generally negative for MT1-MMP mRNA. Th e consistent co-localization of MT1-MMP with MMP-2 and type IV collage n in the same subset of cytotrophoblasts strongly suggests that all th ree components co-operate in the tightly regulated fetal invasion proc ess. The co-expression of MT1-MMP and MMP-2 mRNA in some of the decidu al cells indicates that these cells are also actively involved in the placentation process.