Involvement of fertilization antigen (FA-1) in involuntary immunoinfertility in humans.

Abstract

Sera from immunoinfertile patients (n = 32) and fertile controls (n = 20) were analyzed for cross-reaction with a purified and characterized sperm-specific glycoprotein, the fertilization antigen (FA-1), employing an enzyme-linked immunosorbent assay. The immunoinfertile sera demonstrated a strong reaction with FA-1 when compared with fertile control sera. There was no correlation between the reaction of sera with FA-1 and the titers obtained through the sperm agglutination technique and the sperm immobilization technique. Immunoinfertile sera showed binding with the protein bands in the regions corresponding to FA-1 on Western blots involving sodium deoxycholate-solubilized human sperm. Antigens isolated with immunoaffinity chromatography involving immunoinfertile sera also demonstrated antigen bands corresponding to FA-1 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Of the seven immunoinfertile couples, three that had antibodies to FA-1 in the male as well as female partners demonstrated a block of fertilization (IVF) due to antibodies bound on the sperm surface. The anti-FA-1 antibody activity was detected in serum as well as in follicular fluid and seminal plasma. Immunoinfertile sera that showed an inhibition of human sperm penetration of zona-free hamster ova showed a significant (P < 0.001) increase in penetration rates after absorption with FA-1. These results indicate that sera from immunoinfertile patients had antibodies reacting with FA-1, and these antibodies are involved in the fertilization process.

Antiidiotypic antibodies to sperm in sera of fertile women that neutralize antisperm antibodies.

“…This may be due to differences in antigenic specificities of the antisperm antibodies present in sera ofinfertile women and/or due to the differences in specificities of the ab-2 present in sera of fertile women. Indeed, the sera from various antibody-positive infertile women have been shown to react with a variety ofdifferent spermatozoal proteins on Western blots of detergent-solubilized human sperm preparations ( 10,24,25).…”

“…Interestingly, sera from infertile women and not from fertile women react strongly with FA-1, indicating its involvement in involuntary infertility in humans (10,11 ). The present study was conducted to investigate whether or not sera from fertile and infertile women have antiidiotypic antibodies (ab-2) to antisperm antibodies (ab-1), especially to FA-l antibodies.…”

Fertilization antigen-1: cDNA cloning, testis-specific expression, and immunocontraceptive effects

“…The FA-1 antigen is a glycoprotein of 23 kDa (monomer) that has a ligand activity for ZP3 of oocyte zona pellucida (16)(17)(18)(19)(20) and causes a reduction in fertility of actively immunized female rabbits (21). Interestingly, the FA-1 antigen also is involved in involuntary infertility in humans (22)(23)(24)(25).…”

Treatment and Prognosis of Immunological Factors in Unexplained Male Infertility

“…The presence of these antibodies may interfere with fertilization in the IVF procedure and leads to fertilization failure. Antigenspecific immune absorption that is aimed at a specific antibodies, rather than all immunoglobulins, has been previously shown to be effective in removing and neutralizing anti-FA-1 antibodies in infertile men [85]. Adsorption with FA-1 antigen helps to remove autoantibodies from the cell surface of sperm cells and increases the acrosome reaction rate by 10 %.…”