Abstract

The results of both clinical and experimental studies suggest that immunologic mechanisms may be significant in the pathogenesis of idiopathic infertility. We have defined and preliminarily characterized a number of immunoregulatory genes which control the phenotypic expression of infertility associated with autoimmune disease of the testis. Our studies utilizing the murine model of experimental allergic orchitis have clearly demonstrated that both classical (class II antigens) and nonclassical major histocompatibility complex-linked immune response genes play a central role in controlling disease susceptibility. We have mapped one nonclassical immune response gene, orchitis susceptibility gene-1 (Orch-1), to an interval of ca. 100 kilobases within the H-2S-H-2D region. In addition, immunogenetic analyses have identified two immune suppression genes, Orch-2 and Orch-3, which control active immunoregulatory mechanisms governing the phenotypic expression of disease resistance. The genetic control of autoimmune infertility in this model therefore appears to be polygenic.