Immunological and genetic factors influencing pregnancy and development.

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.