Events that occur in conjunction with implantation of the embryo in rodents include an increase in vascular permeability at the site of implantation, the transformation of stromal cells immediately around the embryo into an avascular decidual zone and the degeneration of the luminal epithelium adjacent to the blastocyst. The loss of the epithelium at this site is an essential part of the implantation process which allows the trophoblast to penetrate the stroma and establish the placenta. The factors responsible for degeneration of the epithelium are unknown. This research proposal is designed to explore the possibility that epithelial cell death may result from either autolytic activity of epithelial cell lysosomes or isolation of the epithelium from its nutritive supply by the primary decidua. To explore the possible role of lysosomes in epithelial cell necrosis, we will determine the number, size, and enzyme activity of the various kinds of lysosomes in the epithelium at implantation sites and non-implantation sites, using morphometric and histochemical techniques at the TEM level. WE WILL ALSO DETERMINE THE EFFECT OF CHLOROQUINE, AN INHIBITOR OF LYSOSOMAL ENZYMES, ON EPITHELIAL CELL DEGENERATION. We will learn whether the primary decidua isolates the epithelium from its nutritive supply be determining the permeability of this zone and the endometrial microvasculature to tracers of various molecular weights. The migration of the tracers, in vivo, will be followed at various times after administration and at several times during the implantation period. The morphological bases of the permeability barriers will be established by studying the types of junctions which are formed between the decidual cells and the types of capillaries present in the endometrium. WE WILL DETERMINE THE EFFECT OF INDOMETHACIN, WHICH BLOCKS THE VASCULAR CHANGES AND DECIDUAL DEVELOPMENT, ON EPITHELIAL CELL DEGENERATION. The results of these experiments will clarify the factors responsible for degeneration of the epithelial cells at implantation and provide us with a better insight into the process of embryo implantation. The scientific disciplines involved are reproductive biology and cell biology.
