PARATHYROID HORMONE-RELATED PROTEIN AND IMPLANTATION

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DESCRIPTION: (Adapted from the applicant s description) Parathyroid hormone-related protein (PTHrP) is a factor which was first isolated from tumors associated with the syndrome of humoral hypercalcemia of malignancy. PTHrP has also recently been identified in a number of normal tissues including the endometrium, myometrium and placenta. Studies have demonstrated that PTHrP is expressed by decidualized stromal cells in the mouse uterus as well as the trophectoderm of blastocysts and acts to stimulate trophoblast outgrowth by mouse blastocysts cultured in vitro. The researchers hypothesize that PTHrP plays an important role in the anchoring and spreading of early trophoblast cells during the process of implantation and that this process involves members of the hedgehog signalling proteins. The specific aims of this proposal are: To determine whether PTHrP acts to increase trophoblast outgrowth by stimulating production of the extracellular matrix proteins fibronectin or laminin or regulates expression of the receptors for these proteins; and whether PTHrP stimulates the secretion of specific metalloproteinases including gelatinases A and B. To determine whether the developing mouse blastocyst and early trophoblast cells express members of the hedgehog signaling proteins and their receptor, and whether the stimulatory effect of PTHrP on blastocyst outgrowth involves this signaling pathway.