We developed a germ-cell specific monoclonal antibody (MA-24) against spermatozoa plasma membrane (Naz et al., Science 225:342, 1984) which blocked human sperm penetration of zona-free hamster ova and inhibited in vitro fertilization of mouse ova by murine sperm without causing agglutination or immobilization of sperm. It recognized a single glycoprotein of testicular origin present on postacrosomes, midpieces and tails of sperm. This fertilization antigen (FA-1) has been isolated from human and murine germ cells using MA-24 immunoaffinity chromatography (Naz et al., Proc. Natl. Acad. Sci., USA, 83:5713, 1986). The overall objective of this project is to characterize sperm-specific antigen (FA-1) and investigate its role in fertilization, embryonic development, implantation and postimplantation fertility in mice. FA-1 will be isolated from murine testes in large amounts by using immunoaffinity chromatography and further purified and characterized for its molecular identity, subunit structure, amino acid contents and carbohydrate composition. The antigenic fragment (polypeptide) of the FA-1 will be isolated by using high performance immunoaffinity chromatography. FA-1 will be checked for its immunogenicity and monoclonal antibodies will be raised reacting against its various antigenic determinants. The fate of antigen after fertilization will be investigated. It will be checked whether MA-24 is directed against carbohydrate or polypeptide portion of the antigenic molecule. We will check the role of FA-1 in fertilization and post-fertilization fertility. We will investigate the cross-reaction of FA-1 with sera from immunoinfertile patients. Besides enabling us to define the molecular events underlying fertilization, embryonic development, and implantation, this project will provide a basis for specific methods for diagnosing and managing involuntary immunoinfertility in humans and development of an anti-sperm contraceptive vaccine.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29HD024425-01A1
Application #
3469887
Study Section
Reproductive Biology Study Section (REB)
Project Start
1988-12-01
Project End
1993-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Lemons, Angela R; Naz, Rajesh K (2012) Birth control vaccine targeting leukemia inhibitory factor. Mol Reprod Dev 79:97-106
Lemons, Angela R; Naz, Rajesh K (2011) Contraceptive vaccines targeting factors involved in establishment of pregnancy. Am J Reprod Immunol 66:13-25
Williams, Ryan M; Naz, Rajesh K (2010) Novel biomarkers and therapeutic targets for prostate cancer. Front Biosci (Schol Ed) 2:677-84
Rodgers-Melnick, Eli B; Naz, Rajesh K (2010) Male-biased genes of Drosophila melanogaster that are conserved in mammalian testis. Front Biosci (Elite Ed) 2:841-8
Naz, Rajesh K; Catalano, Briana (2010) Gene knockouts that affect female fertility: novel targets for contraception. Front Biosci (Schol Ed) 2:1092-112
Naz, Rajesh K; Dhandapani, Latha (2010) Identification of human sperm proteins that interact with human zona pellucida3 (ZP3) using yeast two-hybrid system. J Reprod Immunol 84:24-31
Naz, Rajesh K; Rowan, Shon (2009) Update on male contraception. Curr Opin Obstet Gynecol 21:265-9
Naz, Rajesh K (2009) Status of contraceptive vaccines. Am J Reprod Immunol 61:11-8
Naz, Rajesh K; Engle, Alexis; None, Rajnee (2009) Gene knockouts that affect male fertility: novel targets for contraception. Front Biosci (Landmark Ed) 14:3994-4007
Naz, Rajesh K (2009) Development of genetically engineered human sperm immunocontraceptives. J Reprod Immunol 83:145-50