A sperm-specific glycoprotein, the fertilization antigen (FA-1) has been isolated and characterized from murine male germ cell plasma membranes, tissue-specific but species-cross-reactive monoclonal antibody (MCA) against which blocks fertilization of murine oocytes by murine sperm. FA-1 causes a reduction of fertility in actively immunized female animals and is involved in involuntary immunoinfertility in humans. Recent data indicate that FA-1 has a lectin binding activity, neutralizes sperm ligand activity of purified porcine ZP3, does not have phosphotyrosine residues nor autophosphorylating tyrosine kinase activity and is also involved in sperm capacitation and/or acrosome reaction. It was further found that the functional epitope on FA-1 recognized by the monoclonal antibody is protein and not carbohydrate moiety of the antigen. In these studies FA-1 was purified using MCA-immunoaffinity column, which yielded small quantity of the antigen. To obtain large quantity of recombinant FA-1 required for further studies we propose to clone the murine gene for FA-1. Monoclonal and monospecific polyclonal antibodies against FA-1 will be used to screen the existing murine testis lambdagt11 cDNA expression library, otherwise additional lambdagt11 and lambdaZAPii cDNA expression libraries will be raised for screening. The immunoreactive clones will be subjected to restriction mapping and sequenced. Comparison of the nucleotide sequence with the known peptide sequences of FA-1 will verify the authenticity of the gene. cDNA sequence will be investigated for homology with any known sequence in Genbank and protein library database. The tissue specific expression and chromosomal assignment for FA-1 will be determined. The cDNA insert will be excised from lambdagt11 library, expressed in pGEM-11Zf transcription vector and translated in vitro to obtain unfused protein. The recombinant FA-1 will be immunoaffinity-purified, and investigated for its authenticity and homogeneity using Western blot procedure and SDS-PAGE. Female mice will be immunized against the recombinant FA-1 and sera and vaginal fluids will be analyzed for anti-FA-1 antibodies. The correlation of the antibody titer with the fertility rates will be analyzed and the animals will be kept for one year to study the reversibility of the antifertility effects. These studies will provide basis for investigating the utility of recombinant FA-1 for regulation of fertility and infertility in humans.
| 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 |
| Naz, Rajesh K (2011) Antisperm contraceptive vaccines: where we are and where we are going? Am J Reprod Immunol 66:5-12 |
| 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 |
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