ROLE OF THE MHC IN EARLY MAMMALIAN DEVELOPMENT

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The preimplantation period of embryonic development is crucial for the survival of mammalian species. During this time the fertilized egg goes through a series of cleavage divisions and differentiation events leading to blastocyst formation. Only then can the embryo implant in the uterus and continue its development. During the preimplantation period, embryos express major histocompatibility complex (MHC) antigens of both maternal and paternal origin. There is mounting evidence that many unsuccessful pregnancies are the result of immunological rejection of embryos by their mothers. In the first part of this proposal we will conduct experiments to define exactly which MHC antigens are expressed on embryos, how the synthesis of the MHC antigens is regulated, and which MHC antigens are recognized by the maternal immune system. These data should aid in the long range goal of designing specific inhibitors to reduce pregnancy wastage. The second part of this proposal deals with a gene we discovered about 10 years ago, the MHC-linked Ped (Preimplantation embryo development) gene, which controls the rate of cleavage of preimplantation mouse embryos. We propose to test for linkage of the Ped gene to the Q region of the MHC, and to evaluate the relationship of Ped gene phenotype to embryo survival. With the expansion of in vitro fertilization clinics all over the country, there has been especial recent interest in this gene. As a long- range goal, this work may provide the basis for the identification and understanding of a Ped gene in the human population. Such a discovery could have understanding of a Ped gene in the human population. Such a discovery could have practical applications. For instance, donor sperm could be selected based on the Ped gene phenotypes of the donor and recipient, to maximize the chances of a successful pregnancy either after artificial insemination or in vitro fertilization.