Fertilization antigen (FA-1) is a tissue-specific glycoprotein that is present on sperm of various mammalian species including mouse and man. It has a function in sperm capacitation/acrosome reaction, has a receptor/ligand activity for ZP3 of oocyte zona pellucida (ZP), and has a definite role in immunoinfertility in humans. Human cognate FA-1 antigen undergoes tyrosine phosphorylation and autophosphorylation during capacitation/acrosome reaction and ZP binding. cDNA encoding for murine FA-1 antigen has been cloned and sequenced, and was found to be a novel gene having testis-specific expression, and antibodies to the recombinant murine antigen completely blocked sperm-ZP binding in vitro (Proc Natl Acad Sci USA, 94:4704-4709, 1997). The present proposal has five specific aims.
Specific Aim #1 is to extend the in vitro studies to examine the immunocontraceptive effects of the murine recombinant FA-1 antigen in actively-immunized female mice.
Specific aim 2 is to clone and sequence the human homologue of the murine FA-1 gene. Antibodies (monospecific polyclonal/monoclonal) against the human cognate FA-1 antigen and the murine FA-1 cDNA will be used as probes to screen the human testes cDNA-lgt11 lZAPiilgt 10 libraries. The specific clones will be subjected to restriction mapping and investigated for homology with any known sequence.
Specific aim 3 is to investigate the tissue-specific expression of the human FA-1 gene using Northern blot and RT-PCR procedures.
Specific aim 4 is to study the chromosomal localization of the human FA-1 gene.
Specific aim 5 is to investigate the immunobiological effects of the human recombinant FA-1 antigen. The human recombinant antigen will be obtained by using the glutathione S-transferase fusion system and examined for its interaction with the human ZP3 and for its involvement in immunoinfertility, and its antibodies will be investigated for their effects on sperm function. Besides enabling the PI to study the structure-function relationship, these studies will help them investigate the potential utility of the human recombinant FA-1 antigen is immunocontraception and immunoinfertility 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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