Characterization of Human Sperm Antigens Reacting With Anti‐Sperm Antibodies From an Infertile Female Patient's Serum

Abstract

Identification of sperm antigens that elicit immunoglobulin (Ig) production and knowledge of their roles in sperm transport and fertilization may enhance diagnosis and treatment of immunologic infertility. Sperm antigens recognized by a female patient's serum anti-sperm antibodies were characterized using an indirect immunobead-binding test, immunoblot analysis, and immunochemical labeling. The anti-sperm antibodies' effect on sperm function was evaluated by acrosome induction by calcium ionophore. Immunobeads specific for IgG were bound to the head of 79% of motile donor sperm. Immunochemical labeling of antibody-binding sites was restricted to the plasma membrane over the acrosomal crescent. No labeling was observed on the inner acrosomal membrane of acrosome-reacted sperm. The antibodies reacted with 35-, 40-, 47-, and 65-kd proteins extracted from acrosome-intact donor sperm. Sperm incubated in 1:4, 1:8, 1:16, and 1:32 dilutions of anti-sperm antibody-positive serum had similar rates of spontaneous acrosome reaction and significantly lower rates of ionophore-induced acrosome reaction compared with sperm incubated in control serum. These results suggest that sperm antigens recognized by the patient's serum anti-sperm antibodies are restricted to the acrosomal region of the plasma membrane. The antibodies may impair fertility by compromising the sperm's ability to undergo capacitation and/or acrosome reaction.

Anti-human proacrosin antibody inhibits the zona pellucida (ZP)–induced acrosome reaction of ZP-bound spermatozoa

“…The results on the significant inhibitory effect of the anti-acrosin antibody on the acrosome reaction are in agreement with those describing the inhibition of acrosin activity and ZP-induced AR and sperm-ZP penetration by soybean trypsin inhibitor (25). Moreover, they agree with previous reports showing an impairment on the AR by antibodies from sera of patients receiving infertility treatment (26)(27)(28) or toward other specific proteins, such as actin (29), and with recent findings from our group showing an inhibitory effect of specific anti-acrosin antibodies generated by gene immunization on calcium ionophore-induced AR of murine spermatozoa (Veaute et al, unpublished observations). The AcrC5F10 antibody appears to be unable to access proacrosin molecules in noncapacitated intact sperm cells (6); membrane vesiculation may have occurred, as described in acrosin-deficient mice (16), allowing the antibody to access the proenzyme pool stored in the acrosome and inhibiting its activation.…”

Anti-ACTL7a antibodies: a cause of infertility

“…The production of antispermatozoa antibodies can cause infertility (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”

Molecular Characterization of Sperm Antigens with In Vivo Developed Antisperm Antibodies in Variably Inseminated Cross Bred-Heifers/Cows

“…Only two polypeptides out of 16 sperm polypeptides reacted with blood serum of infertile cows [15]. Circulating anti-sperm antibodies in blood serum of infertile patients also reacted with 4 surface antigens of 35, 40, 47 and 65 kDa [10].…”

“…During cryopreservation of semen, antigenic structure of sperm cell is changed due to addition of extender, freezing/thawing procedures and seminal plasma is also significantly reduced during semen preparation for AI. The varying degree to which the antibodies impair fertilization suggests that identification of relevant sperm surface antigens and their role in the fertilization process would lead to formulation of an effective therapeutic plan to treat infertility [10]. It was also demonstrated by Jawad [11] that elevated level of ASA can be treated with zinc sulfate.…”