Sperm and gestational tissues can stimulate responses, and such responses have been associated with infertility in experimental animals and humans. Until recently, reproductive immunology has focused on the role of antibodies in immunologic infertility. It is now possible using new immunological reagents such as monoclonal antibodies to lymphocyte phenotypic markers and purified lymphokines and monokines, to probe cellular immune mechanisms that may also affect reproductive functions. Recently, we and others have reported that soluble products of activated leukocytes inhibit human sperm motility and fertilization functions. The objective of this project is to establish a mouse model of anti-sperm cell-mediated immunity (CMI) and to use this model to further study the effects of cellular and soluble mediators of antisperm CMI responses on sperm function in vitro and in vivo. Mice will be actively immunized at various sites (ie-intrauterine, intraperitoneal, intramuscular) with epididymal sperm emulsified in adjuvants that predominantly stimulate CMI responses, or passively immunized by transfer of activated T cells from immunized syngeneic donors. Uterine and cervical T cell and macrophage populations will be monitored by immunohistologic technique in a time course following active or passive immunization and subsequent exposure to sperm (booster immunization, mating). Fertility will be assessed in vivo in actively and passively immunized and control groups by 1) enumeration of 2 cell embryos, and 2) enumeration of implantation sites. Local lymphokine and monokine production will be assessed in immunized control groups by 1) application of antibodies directed against specific lymphokines and monokines to cervical/uterine sections using the immunoperoxidase technique, and 2) quantitation of specific lymphokines and monokines in uterine flushings using ELISA technique. Furthermore, studies will be performed ont he effects of leukocyte supernatants and individual lymphokines and monokines on mouse sperm motility, viability and egg penetration ability in vitro. These studies should provide insight into cellular immune mechanisms underlying infertility, and may suggest approaches to enhance the efficacy of contraceptive vaccines.
| Fulop, V; Feinberg, B B; Steller, M A et al. (1992) Molar villous fluid suppresses mononuclear cell cytotoxicity. Gynecol Oncol 47:311-6 |
| Haimovici, F; Takahashi, K; Anderson, D J (1992) Antifertility effects of antisperm cell-mediated immunity in mice. J Reprod Immunol 22:281-98 |
| Fulop, V; Steller, M A; Berkowitz, R S et al. (1992) Interferon-gamma receptors on human gestational choriocarcinoma cell lines: quantitative and functional studies. Am J Obstet Gynecol 167:524-30 |
| Haimovici, F; Hill, J A; Anderson, D J (1991) The effects of soluble products of activated lymphocytes and macrophages on blastocyst implantation events in vitro. Biol Reprod 44:69-75 |
| Wolff, H; Politch, J A; Martinez, A et al. (1990) Leukocytospermia is associated with poor semen quality. Fertil Steril 53:528-36 |
| Anderson, D J; Hill, J A (1988) Cell-mediated immunity in infertility. Am J Reprod Immunol Microbiol 17:22-30 |
