A major site of impaired fertility in men with autoimmunity to sperm rests at the level of restricted sperm entry and motion within cervical mucus. We studied the effects of a protease derived from Neisseria gonorrhoeae, whose substrate specificity is limited to human IgA1, on the ability of antibody-bound sperm to penetrate human cervical mucus in vitro. IgA on the sperm surface, but not IgG, was degraded by IgA1 protease. A correlation was seen between the levels of IgA bound relative to IgG and the improvement in sperm cervical mucus penetrating ability after IgA1 protease exposure. These results provide evidence that antisperm autoantibodies of both IgA and IgG classes impair the ability of spermatozoa to populate the female reproductive tract. They implicate the Fc region of the immunoglobulin molecule in mediating this effect and offer the potential to restore male fertility by treating antibody-bound sperm in vitro with immunoglobulin-directed bacterial proteases, before insemination.
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