Regulation of urokinase plasminogen activator production in implanting mouse embryo: Effect of embryo interaction with extracellular matrix

Embryo implantation in the mouse is an invasive process and requires the action of proteinases, including plasminogen activator (PA) and metalloproteinases. After the implanting embryo establishes close contact with the endometrium, the invasion process begins, at least in part, through interactions of the embryo with the extracellular matrix in the endometrium. This study determined whether embryo interaction with extracellular matrix components would affect the secretion of PA in vitro. Mouse embryos were collected from the uterus on Day 3.5 of development, just before implantation, and were cultured on culture dishes precoated with bovine serum, plasma fibronectin, or BSA (control). Embryos cultured on serum- or fibronectin-coated dishes secreted significantly more PA than those cultured on BSA. The effect of fibronectin was inhibited by hexapeptides that contained the integrin-recognizing Arg-Gly-Asp sequence. This indicates that the action of fibronectin in enhancing PA secretion is mediated through its receptor (integrins) in the embryo. Fibronectin fragments reproduced the effect of the whole fibronectin molecule, suggesting that the clustering of integrins by specific ligands is responsible, at least in part, for the increased PA secretion. The increase in PA secretion was e specific response to fibronectin rather than a reflection of increased total protein secretion, and was at least partially a result of the increased steady state level of PA mRNA in the cultured embryos. Laminin was as effective as fibronectin in promoting PA secretion. Epidermal growth factor increased PA secretion, probably by promoting the interaction of the embryos with the extracellular matrix. In summary, our findings indicate that the interactions of the implanting embryos with their extracellular matrix may regulate trophoblast invasion by controlling PA secretion.