We propose to continue producing and characterizing monoclonal antibodies to human spermatozoa, and isolating antigens from the relevant monoclonal antibodies. Such antigens have possible uses as an immunocontraceptive vaccine, immunodiagnosis of infertility, and the study of various fertilization and ontogenic processes. Our goal is to establish a bank of hybridoma cell lines specific to the cell surface of germ cells and relevant to the isolation of specific antigens. We will characterize monoclonal antibodies: (1) immunohistologically, to localize and follow the fate of individual molecular species on sperm; (2) biochemically, to determine the molecular identities of the antigenic molecules; (3) in functional assays--such as (a) sperm immobilization, (b) agglutination, (c) in vitro cervical mucus penetration, and (d) hamster ovum penetration--to determine if they affect the ability of sperm to penetrate eggs; (4) to determine their effects on fertility in in vitro and in vivo systems; and (5) with affinity chromatography, to isolate the specific antigens involved and then to characterize them and check their utility for immunodiagnosis and contraception. We will use the monoclonal antibodies: (1) to compare sperm iso- and autoantigens in serum and seminal plasma from infertility patients and vasectomized men and (2) to artificially inseminate mice and rabbits by means of sperm treated with monoclonal antibodies which react to the sperm of these species or to immunize them, passively or actively, to more thoroughly evaluate the role of antisperm antibodies in infertility. Sperm-specific monoclonal antibodies will enable us and others to define the mechanisms underlying fertility. Thus, we shall build a foundation for new approaches in the diagnosis of infertility, treatment of infertile patients, and development of better immunocontraceptives.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD014572-03A1
Application #
3312673
Study Section
Reproductive Biology Study Section (REB)
Project Start
1981-08-01
Project End
1987-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Oregon Regional Primate Research Center
Department
Type
DUNS #
City
Beaverton
State
OR
Country
United States
Zip Code
97006
Alexander, N J (1988) The effects of antibody sperm-egg interaction. Ann N Y Acad Sci 541:317-23
Kurpisz, M; Simon, L L; Alexander, N J (1987) EBV transformation and microfusion as the potential source of human monoclonal antisperm antibodies. Am J Reprod Immunol Microbiol 15:61-5
Ben, K; Alexander, N J; Huso, N (1986) In vitro cell-mediated and complement-mediated cytotoxicity to murine testicular cells. Am J Reprod Immunol Microbiol 12:33-7
Berkowitz, R S; Alexander, N J; Goldstein, D P et al. (1985) Reactivity of anti-human sperm monoclonal antibodies with normal placenta, hydatidiform mole, and gestational choriocarcinoma. Gynecol Oncol 22:334-40