Gill T J
Am J Reprod Immunol Microbiol. 1986 Mar;10(3):116-20.
Hypotheses concerning reproductive competence focus on immunological and genetic mechanisms. The immunological hypothesis involves arguments that an immune response is necessary for implantation (or at least increased reproductive capacity), the antibody response to the placental antigens is composed of "blocking" antibodies, immunosuppressive factors are produced during pregnancy, and HLA antigen sharing in humans having chronic spontaneous abortions (CSA) causes a decreased immune response. The most potent antigen on the placenta is a class I molecule different from the classical transplantation antigens: Pa in the rat and TLX in the human. The genetic hypothesis states that CSA may be due to the presence of major histocompatibility complex (MHC)-linked, recessive lethal genes in the fetus and that the sharing of HLA antigens is just a marker for this segment of chromosome. Recessive lethal genes linked to the MHC exist in mice and rats and possibly in humans. They could act by themselves to cause fetal loss, or they could act epistatically with nonMHC lethal genes. This type of interaction occurs in the rat between the MHC-linked grc and Tal or Hre. Recent work in our laboratory has shown that the grc also increases susceptibility to the development of cancer following the feeding of a chemical carcinogen. This unique finding presents a new and powerful approach to exploring the relationship between embryogenesis and carcinogenesis.
关于生殖能力的假说主要集中在免疫和遗传机制方面。免疫假说认为，免疫反应对于着床（或至少对于提高生殖能力）是必要的，对胎盘抗原的抗体反应由“封闭”抗体组成，孕期会产生免疫抑制因子，并且患有习惯性自然流产（CSA）的人类中HLA抗原共享会导致免疫反应降低。胎盘上最有效的抗原是一种与经典移植抗原不同的I类分子：大鼠中的Pa和人类中的TLX。遗传假说指出，CSA可能是由于胎儿中存在与主要组织相容性复合体（MHC）连锁的隐性致死基因，并且HLA抗原共享只是该染色体片段的一个标记。与MHC连锁的隐性致死基因存在于小鼠和大鼠中，也可能存在于人类中。它们可能单独起作用导致胎儿丢失，或者与非MHC致死基因发生上位性相互作用。这种类型的相互作用在大鼠中发生在与MHC连锁的grc和Tal或Hre之间。我们实验室最近的研究表明，喂食化学致癌物后，grc还会增加患癌易感性。这一独特发现为探索胚胎发生与致癌作用之间的关系提供了一种全新且有力的方法。
