[Frontiers in Bioscience 3, e39-48, April 30, 1998]
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CAVEAT LECTOR




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TESTIS - SPECIFIC PROTEINS AND THEIR ROLE IN CONTRACEPTIVE VACCINE DEVELOPMENT

Rajesh K. Naz and Cynthia M. Vanek

Division of Research, Department of Obstetrics and Gynecology, Medical College of Ohio, Richard D. Ruppert Health Center, 3120 Glendale Avenue, Toledo, OH 43614-5809, USA

Received 3/30/98 Accepted 4/27/98

2. INTRODUCTION

Sperm antigens are attractive candidates for the development of a contraceptive vaccine. The rationale and feasibility of using sperm antigens in immunocontraception is provided by the following findings. Deliberate immunization of male or female animals of various species (1-3) including humans (4, 5) with autologous or isologous spermatozoa results in infertility. The data of vasectomy and involuntary infertility in humans also provide strong evidence for the antisperm contraceptive approach. Up to 70% of vasectomized men form antisperm antibodies (ASA) (6) and up to 30% of infertility may be associated with the presence of ASA in the male and/or female partner of an infertile couple (7). These data indicate that the spermatozoon has both auto- as well as isoantigenic potentials, and when sufficient antibody titers are present, it can cause infertility in humans.

Although whole spermatozoon can produce an antibody response that is capable of inducing infertility in humans, they cannot per se be employed for the development of a vaccine (8,9). Besides the presence ofnumerous ‘internal’ antigens common with somatic cells, there are several proteins on the sperm cell surface that are likely to be shared with various somatic cell plasma membrane. The spermatozoon has antigens that can be shared with antigens on brain (10, 11), kidney (10), erythrocyte (12), lymphocyte (13), embryo (14) and oncofetal antigens (15). Sperm antigens can also react with soluble proteins such as lactoferrin and other proteins present in body fluids such as milk, serum, and saliva (16). Some of these cross-reacting antigens have been characterized. A nervous system antigen (NS-6) has been delineated on the cell surface of brain, kidney, and sperm cell (10); D2 adhesion protein is present on both brain and testicular cells (18); and F-9 antigen is present on sperm, embryo, and teratocarcinoma cells (19).

Thus, only those proteins that are testis/sperm-specific can be employed for the development of an antisperm contraceptive vaccine (ACV). The utility of a sperm antigen in immunocontraception is contingent upon its: 1. Testis/sperm-specificity, 2. Role in spermatogenesis and/or fertilization, and 3. Accessibility to the antibody action. Also, the antigen should be capable of raising enough antibody titer, especially in the genital tract, to have a contraceptive effect. The aim of the present article is to review and update the information regarding the proteins that have been reported to be testis/sperm-specific and may have potential application in the ACV development. Specifically, the tissue-specific antigens expressed on mature sperm cell and developed during later stages of spermatogenesis will be reviewed in this article. The proteins that are added onto spermatozoon during its transit through the epididymis and vas deferens and through exposure to secretions of various accessory glands are not included in this review.