Immunologic basis of reproductive failure

This article has reviewed the immunologic factors of human infertility and some of the animal models that have provided experimental evidence for the better understanding of these disorders. It is clear that definitive evidence for human autoimmune diseases of the gonads is still lacking. However, recent findings in infertile men represent tangible support for this possibility and should stimulate further studies. Insofar as these diseases are relatively rare, meaningful clinical investigations can best come from a multicenter effort based on patients with well-defined clinical and laboratory profiles. To arrive at a firmer immunologic basis for these human diseases, it will be helpful to extrapolate from experimental studies. For both testicular and ovarian diseases, it will be desirable to refine the methods for quantifying humoral and cellular immune responses to the organ-specific autoantigens in the testis and ovary. Immunohistochemical localization of immune reactants is likely to be successful when performed early in the disease process and on tissue from patients with active disease. The nature of the immune deposits in testes will need to be confirmed by the classic approach of elution of antibody from the tissue with dissociating agents, followed by quantitation. The large quantity of tissue required for study can come from orchiectomy specimens from infertile men with unilateral vasal stenosis. In addition to immunologic reactions that lead to inflammation, future studies should take into consideration the possible existence of autoantibodies that react against hormone receptors or other functional ligands involved in ovarian or testicular physiology. Despite the paucity of evidence for human autoimmune diseases of the gonads, the likelihood of existence of these diseases is also supported by the ease with which experimental autoimmune disease of the gonads can be induced. We have described the experimental models of gonadal autoimmune diseases in detail, since analysis of these diseases has led to some unique contributions to immunopathology research and the physiology of the gonads. It is anticipated that future studies will characterize the target antigens as well as the local and systemic mechanisms that prevent autoimmune disease of the gonads in normal individuals. Moreover, it is anticipated that the model of neonatal thymectomy and oophoritis/orchitis will help to define the intricate interplay among thymic function, tolerance mechanisms, and autoimmunity. It is important to emphasize that research on the maternal-fetal immunologic relationship is a rapidly moving and controversial field. Although we have tried to point out controversial areas, the reader may wish to consult several excellent recent reviews. The anatomy and function of the hemochorial placenta and decidua are extraordinarily complex.(ABSTRACT TRUNCATED AT 400 WORDS)