Reproductive Immunology: Past, Present, and Future

REPRODUCTIVE IMMUNOLOGY; PAST, PRESENT, AND FUTURE RUPERT E. BILUNGHAM* and ALAN E. BEERi The present decade has witnessed the burgeoning of some interrelated basic and clinical studies we have come to know as "the immunobiology of reproduction." Directly or indirectly, immunology has now intruded into, or been shown to underlie, nearly every aspect of mammalian reproduction [I]. It may be the basis of a natural defense mechanism or of a disease process, it may afford an approach to the artificial control of certain reproductive processes, it may furnish an experimental approach to an investigation, and it may be the basis of a clinical assay procedure (e.g., as in radioimmunoassays). The purpose of this article is to present an overview of the origins, scope, and some of the achievements and potentialities of reproductive immunology. We shall also indicate the significant impact certain discoveries in reproductive immunology have had on the development of immunology in general. "In the Beginning": Early Observations on Immunologically Based Phenomena in Reproductive Biology Man's first experience of immunological phenomena associated with reproduction must have been gained unwittingly from observations on members of his own species as well as on his domestic animals. For example, he must have been aware ofthe frequent association oforchitis with mumps in mature but not in prepubertal males and that damage to one testicle often led to developmentoflesions in the other (probably the expressions of an autoimmune response against distinctive components of the mature male gonad). He must surely have encountered infertility and abortion and observed hemolytic disease of the newborn human as •University ofTexas Health Science Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235. tUniversity of Michigan Medical School, Ann Arbor, Michigan 48109.© 1984 by The University of Chicago. AU rights reserved. 0031-5982/84/2702-0376101.00 Perspectives inBiology and Mediane, 27, 2 · Winter 1984 \ 259 well as a similar disease affecting suckling colts and mule foals. He must have recognized the indispensable protective properties ofcolostrum for the newborn ungulate for which ordinary milk is no substitute. Furthermore , the increased susceptibility of pregnant women to smallpox and tuberculosis and the remission of symptoms of rheumatoid arthritis and possibly of lupus and certain other diseases of suspected autoimmune etiology during pregnancy cannot have escaped his attention. Early scientific observations of immunological significance made "before their time" include William Hunter's (famous "man midwife" and anatomist of eighteenth-century London and author of the classic "Anatomy of the Gravid Uterus") demonstration that the placenta develops from the chorion and decidua and, more important, that the fetal circulation is at all times completely quarantined from that ofits mother. In 1871, Charles Darwin appeared to be moving toward an immunological explanation for infertility when he related reduced fertility to profligacy in women. Another early immunological landmark was Heape's successful transfer of allogeneic blastocysts to surrogate mother rabbits in 1890. This established that the success of the conceptus as an allograft required absolutely no genetic contribution from the mother [2]· RECOGNITION OF ANTIGENS OF THE MALE REPRODUCTIVE SYSTEM The beginning of the twentieth century saw many primordial immunologists successfully seeking evidence of antigenicity, in terms of host responses to readily available spermatozoa, seminal plasma, and other testicular material. Evidence was also obtained that infertility in experimental animals, unequivocally in males but rather equivocally in females, is inducible by inoculation with seminal or testicular material. From these crude early beginnings arose attempts in man to procure infertility in both sexes by immunological means and to account for clinical infertility in both sexes in immunological terms [3]. For immunologists in general, experimental allergic orchitis soon became a classic, much studied, example or model of an organ-specific autoimmune disease. Important developments in this still very active and important field include: (1) the introduction of adjuvants to heighten host responses to the autoantigens concerned and facilitate their identification in biochemical terms; (2) localization of these antigens ; (3) recognition that spermatozoa express segregating transplantation alloantigens in addition to autoantigens, so that ejaculates confront females with both an alio- and an autoantigenic stimulus; (4) identification ofthe blood/testis barrier at the ultrastructural level and recognition of its immunological protective significance for developing germ cells; and (5) thorough appraisal...