Our laboratory is interested in understanding the mechanisms involved in the regulation of trophoblast cell differentiation and invasion into the uterine stroma during the implantation process. We are focusing on the role of two proteins, parathyroid hormone-related protein (PTHrP) and EMMPRIN, in regulating extracellular matrix production and metalloproteinase activity in the implantation site. PTHrP has been shown to regulate matrix production and stimulate angiogenesis in bone. We have found that PTHrP is expressed not only by specific uterine cells at the time of implantation but also by the differentiating blastocyst. EMMPRIN is a membrane bound protein that stimulates metalloproteinase (MMP) production by surrounding cells and also acts as a binding protein for specific MMPs. Transgenic knockout mice are being used to study the roles of these proteins around the time of implantation.