We shall study some of the biochemical interactions which occur between the preimplantation blastocyst and the endometrium which allow for the establishment of pregnancy. We plan to purify two early products of the sheep conceptus. One of these (Proteir X), a low molecular weight protein, is released, during a restricted period of development during which maternal recognition of pregnancy occurs. It can be purified from the medium after culturing whole conceptuses in vitro using ion-exchange and gel filtration chromatography. The protein is taken up by the uterine epithelium where specific membrane receptors appear to exist. We shall investigate whether introduction of Protein X into the uterine lumen of Day 12-14 non-pregnant ewes leads to maintenance of corpus luteum function or induction of a state of pseudopregnancy. We plan to measure effects on endometrial protein synthesis, particularly on the production of secreted proteins, in a quantitative manner and determine whether it influences the pattern of endometrial steroid or prostaglanding metabolism. Finally, we shall test whether the protein is mitogenic. The second sheep blastocyst product is a large glycoprotein. We propose to detect its site of synthesis and deposition by immunocytochemical techniques and determine whether it is immunosuppressive towards sheep lymphocytes by means of in vitro tests. In a second area of study, we plan to study whether spherical pig blastocysts are able to elongate and develop normally in vitro when cultured in reconstituted uterine secretions. Such studies will allow us to investigate the mechanism of cellular reorganization and understand the role of maternal secretory products in blastocyst development. A final project is to study whether the progesterone-induced protease inhibitors secreted by the uterine endometrium control blastocyst invasiveness. This will be achieved by transferring Day 12 blastocysts to uteri not producing inhibitor to determine whether they can then invade. We shall also measure whether blastocysts can degrade components of the extracellular matrix of cultured cells. These experiments may define some of the parameters which control trophoblast inevasiveness.
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