ROLE OF THE MHC IN EARLY MAMMALIAN DEVELOPMENT

胚胎发育的植入前期是至关重要的 哺乳动物物种的生存。 在此期间 受精卵经过一系列的卵裂分裂， 导致胚泡形成的分化事件。 只有这样 胚胎能否植入子宫并继续发育 发展 在植入前期，胚胎表达 主要组织相容性复合体（MHC）抗原 母亲和父亲的起源。 有越来越多的证据表明 许多不成功的怀孕是免疫的结果。 母亲对胚胎的排斥。 第一部分 建议我们将进行实验，以确定究竟是什么 MHC抗原在胚胎上表达， MHC抗原受到调控，哪些MHC抗原 由母体免疫系统识别。 这些数据应 有助于设计特异性抑制剂的长期目标， 减少怀孕浪费。 这个提议的第二部分涉及我们发现的一个基因 大约10年前，MHC连锁的Ped（植入前胚胎） 发育）基因，该基因控制切割的速率， 植入前小鼠胚胎 我们建议测试 的Ped基因的MHC的Q区，并评估 Ped基因表型与胚胎存活的关系 与 在全国范围内扩大体外受精诊所， 近来人们对该基因特别感兴趣。 作为一个长期的- 范围目标，这项工作可以提供识别的基础 以及对人类中Ped基因的了解。 这样的 这一发现可能有助于了解人类中的Ped基因， 人口 这样的发现可能有实际应用。 例如，可以根据Ped来选择供体精子。 供体和受体的基因表型，以最大限度地 成功怀孕的机会，无论是人工流产后， 人工授精或体外受精。

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.