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 t he action of proteinases, including plasminogen activator (PA) and met alloproteinases. 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 th e endometrium. This study determined whether embryo interaction with e xtracellular matrix components would affect the secretion of PA in vit ro. Mouse embryos were collected from the uterus on Day 3.5 of develop ment, just before implantation, and were cultured on culture dishes pr ecoated with bovine serum, plasma fibronectin, or BSA (control), Embry os cultured on serum- or fibronectin-coated dishes secreted significan tly 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 enh ancing PA secretion is mediated through its receptor (integrins) in th e embryo, Fibronectin fragments reproduced the effect of the whole fib ronectin molecule, suggesting that the clustering of integrins by spec ific ligands is responsible, at least in part, for the increased PA se cretion, The increase in PA secretion was a specific response to fibro nectin rather than a reflection of increased total protein secretion, and was at least partially a result of the increased steady-state leve l of PA mRNA in the cultured embryos, Laminin was as effective as fibr onectin in promoting PA secretion. Epidermal growth factor increased P A 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.