Antisperm Antibodies Associated with Infertility: Properties and Encoding Genes of Target Antigens

Abstract

Abstract. Infertility among couples of reproductive age is a perplexing condition when the cause is indeterminate. These cases are classified as unexplained infertility. In a subset of subjects, antisperm antibodies with sperm agglutinating and/or immobilizing activities have been detected in the blood or fluids of the reproductive tract. These cases are designated as immunologic infertility although a cause and effect relationship of the antibodies to infertility has not been established. In this review, seven target sperm antigens to antibodies associated with infertility and their encoding genes are described. The antisperm antibodies (ASAs) examined were obtained from infertile women or were monoclonal antibodies (mAb) raised against human sperm proteins. All the ASAs studied possessed potent sperm agglutinating and/or immobilizing activities. The target antigens were isolated from human and other mammalian sperm, and the encoding genes identified. The seven antigens are YWK‐II, BE‐20, rSMP‐B, BS‐63 (nucleoporin‐related), BS‐17 (calpastatin), HED‐2 (zyxin), and 75‐ kDa. Each antigen is a distinct and separate entity and is produced by different cells of the reproductive tract, (e.g., germ cells, epididymal epithelial cells, and Sertoli cells). No single predominant target component has been found to interact with the ASAs. It is proposed that immunologic infertility is the consequence of the combined actions of multiple ASAs in immobilizing and/or agglutinating spermatozoa, blocking spermegg interaction, preventing implantation, and/or arresting embryo development.

Sertoli Cell-Specific Deletion of the Androgen Receptor Compromises Testicular Immune Privilege in Mice1

“…Our findings are similar to those of Qu et al [38] in which injections of syngeneic testicular germ cells without adjuvants or bacterial components resulted in antibodies recognizing antigens of 15-200 kDa specific to round spermatids. Together, these findings may contribute to ongoing efforts to identify prominent germ cell antigens for use as diagnostic biomarkers or relevant targets for contraceptive vaccines [39,40].…”

Acrosin antibodies and infertility. I. Detection of antibodies towards proacrosin/acrosin in women consulting for infertility and evaluation of their effects upon the sperm protease activities

“…The ASA have been found to differentially bind to capacitated sperm cells (9,10) and to affect several gamete functions, such as survival and motility (11), acrosomal exocytosis (12)(13)(14), and gamete interaction (15)(16)(17)(18); in addition, evidence suggesting a detrimental effect of ASA on early development of human and mouse embryos has been reported (19)(20)(21). Despite its relevance, the relationship between the presence of ASA and its effect on fertility has remained difficult to establish; this is, at least in part, due to variations in serum concentrations of antibodies in infertile patients (3) as well as to ASA complexity, most likely comprising a vast repertoire of antibodies interacting with multiple sperm components (3,22,23). Although in many cases an impairment of sperm functions has been demonstrated, not all ASA will alter them, because either the antigen is not directly involved in a sperm biologic process or the antibodies do not bind to a functional domain of the antigen, as previously suggested (23).…”

Testicular tumors as a possible cause of antisperm autoimmune response

“…Studies have demonstrated that ASA can interfere with the fertilizing ability of spermatozoa, affecting both sperm motility in the semen and their ability to pass through female genital secretions, the fusion of the gametes (a key event of fertilization), and possibly the first step of embryo development (13)(14)(15).…”