Abstract

PIP: Isozyme study can provide useful information on structure-function relationships, biological specificity, gene regulation, and evolution. This paper reviews the isozyme lactate dehydrogenase (LDH)-C4, the product of a 3rd gene locus whose expression is restricted to the testis. A precise correlation between active spermatogenesis and LDH-C4 synthesis has been established, and the genes that encode sperm-specific enzymes have been shown to be under coordinate control. LDH-C4 does not appear until puberty and then is isolated from the immune system by the blood-testis barrier. The strong immune response to LDH-C4 and its unique genetic regulation and biological specificity suggest its potential as an alternative contraceptive technology. Humoral or cell-mediated immunity to the isozyme could have an adverse effect on sperm function, preventing fertilization. Female baboons immunized with LDH-C4 showed a substantial immune response as measured by circulating antibody titer and had 80% fewer offspring than nonimmunized animals when mated. The antibody is available along the route travelled by sperm and at the site of fertilization in the oviduct. Antibody in cervical mucus, uterine fluids, and oviducal fluids combines with LDH-C4 on the sperm surface and impedes the progress of the male gamete, presumably by agglutination. The immunosuppression of fertility appears to be related to the antibody titer and number of injections. The effect is reversible. These findings encourage further studies to develop LDH-C4 as a contraceptive vaccine. However, its efficacy must be increased and the natural product replaced with a snythetic antigen. Several small peptides bearing an antigenic determinant of LDH-C4 (e.g., MC 5-16, MC 152-159, MC 211-220, MC 101-115) have induced an immune response to mouse LDH-C4. Although the response is quantitatively less than that obtained after immunization with the natural protein, there is significant synthesis of specific antibodies. Further manipulations of the dosage, route of immunization, and schedule of these peptides are required to ensure maximum synthesis.