The Immunophysiology of Male Reproduction

There is a close functional relationship between the male reproductive and immune systems. Immunological responses against sperm antigens or other elements of the reproductive tract can lead to androgen insufficiency, infertility, or chronic inflammation. Systemic or local immune activation and inflammation directly inhibit the hypothalamic-pituitary-Leydig cell axis, interfere with spermatogenic cell development, and may provoke sperm antibody formation. Traditional explanations for protection of spermatogenic cells, based on physical barriers or immune cell exclusion, are not consistent with either the organization of the reproductive tract or modern concepts of immunoregulation. Regulation of immune responses in the male reproductive tract involves immunoregulatory macrophages and lymphocytes, as well as active somatic cell suppression of antigen-specific immunity by anti-inflammatory and immunosuppressive factors, including cytokines and androgenic steroids. These restraints on antigen-specific immune mechanisms appear to be counterbalanced by enhanced innate immunity. Finally, inflammatory signaling pathways appear to play an important role in normal male reproductive function, and there is evidence that establishment of male reproduction during development is intimately linked to the maturation of the local immune environment.