The long range objective of this project is to understand the processes involved in interaction of the trophoblast and endometrium during implantation. Advances in our understanding of the endocrine control of pregnancy and of in vitro fertilization in the human have not been paralleled by increased understanding of implantation, due in part to a lack of information concerning early implantation and of suitable in vivo and in vitro models.
Our first aim i s based on our hypothesis that different types of trophoblast play different roles in implantation, and that consequently the extent and duration of a given type of trophoblast, and endometrial responses to these types, determine the nature of the implantation process. To examine the characteristics of trophoblast participating in implantation in nonhuman primates, immunocytochemical methods will be used to localize intermediate filament types in early implantation stages obtained from cynomolgus or rhesus monkeys. Distribution of antibody to chorionic gonadotropin and to factor VIII-related antigen, and the distribution of lysosomal constituents will also be used to determine differences in origin and function of the different trophoblast types. In vitro incorporation of 3H thymidine and 3H leucine will be used to determine the potential for cell replication and growth. Several methods will be used to examine in vitro interactions with specific matrices. The studies of trophoblast types are expected to correlate with numerous studies concerning trophoblst cells derived from first trimester human placentas. They should clarify what aspects of the implantation process in nonhuman primates are similar, different, or exaggerated, compared with the human. To characterize the first adhesion between trophoblast and uterine luminal epithelium, initial adhesion and epithelial penetration stages will be obtained from cynomolgus monkeys. To model interactions between trophoblast and uterine epithelium, rat trophoblast cells will be exposed in vitro to different polarized epithelia. To examine the role of decidual cells in implantation, decidual cell interactions with extracellular matrix will be examined in vitro, and the nature of the interaction with basal laminas will be explored using immunocytochemical methods. Structural methods will be used to examine the manner in which trophoblast penetrates capillaries in the primate, and the manner in which pathways for maternal blood are established in the rat. To continue studies of differentiation prior to implantation, and attempt will be made to follow the fate of individual blastomeres using differential interference contrast or vital fluorescent dyes. Studies concerning formation of the primate embryo will focus on the origin of intraembryonic endoderm and mesoderm.
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