The ovary as an immune target

The ovary does not have a distinct morphologic barrier between the immune s ystem and the developing gametes. This is in contrast to the testis in whic h the junctional complexes between the Sertoli cells form the blood-testis barrier. Whereas there are numerous factors, including genetic ones, associ ated with ovarian dysfunction, the immune factors have frequently been impl icated in ovarian dysfunction. Much of our knowledge used to evaluate the i mmune system of the ovary has come from studies on the expression of the zo na pellucida (ZP) proteins during ovarian development. Initial studies by D unbar and colleages(1,2) demonstrated that immunization of rabbits with por cine ZP proteins (but not rabbit ZP proteins) would result in the generatio n of antibodies that inhibit sperm binding to the ZP and interfere with nor mal ovarian follicular development. In contrast to the rabbit and primate models, immunization of mice or rats with porcine ZP proteins does not have an effect on fertility or ovarian fu nction although immunization of certain strains of mice with mouse ZP pepti des and immune activator systems has been shown to result in ovarian pathol ogy. Whereas immune inflammatory reactions have been observed in the mouse models, no such immune reactions have been observed in rabbit, guinea pig, or nonhuman primate models. Subsequent observations in nonhuman primates have shown that immunization o f primates with ZP proteins expressed from cDNAs coding for the mouse and r abbit ZP2 (the mouse homologue has 60% amino acid identity ti human ZP2) or the mouse ZP3 (the mouse protein has 67% amino acid identity with human ZP 3) causes ovarian dysgenesis. In contrast, immunization of primates with re combinant rabbit ZP1 protein (the mouse homologue has 39% amino acid identi ty with human ZP1) does not affect nonhuman primate ovarian function or fol licular development but will elicit antibodies that inhibit sperm binding t o the primate ZP. These studies have collectively provided important inform ation concerning the immunologic status of the ovary and demonstrate the sp ecies variations in immune responses to different ovarian immunogens. (J So c Gynecol Investig 2001;8:S43-S48) Copyright (C) 2001 by the Society for Gy necologic Investigation.