Temporal Appearance of Antisperm Autoantibodies in Lewis Rats Following Vasectomy

Unilateral obstruction or injury to the vas deferens can result in significant injury to the contralateral testicle. Antisperm autoantibodies are thought to play a significant role in this phenomenon. It has been reported that early surgical repair of the vas, before the development of antisperm autoantibodies, will prevent any potential damage to the contralateral testicle. This led us to investigate the timing of the antisperm antibody production and to attempt to determine whether antibody production precedes histologic testicular damage in the Lewis rat model. In a controlled study, mature rats were divided into temporal groups, with the experimental animals all receiving a unilateral vasectomy. At postoperative endpoints of 1, 7, 15, or 30 days, blood samples were collected for immunologic assay, and the testicles were harvested for histologic examination. Antibody levels were measured by an immunobead test using goat anti‐rat immunoglobulin G (IgG)‐coated Sepharose beads; tissue sections were fixed in Bouin solution, embedded in paraffin, and stained with hematoxylin and eosin. There was no statistically significant histologic difference between any of the groups. However, immunologic evaluation revealed a statistically significant increase in immunobead antibody binding in the 30‐day group compared to the control groups (P = .02). These data seem to indicate that in this model, antisperm antibody production is not evident until 15–30 days after unilateral injury to the vas deferens occurs, and the development of these antibodies precedes any demonstrable histologic damage to the testicle. If it is correct to infer that human antisperm antibody production will also precede histologic testicular damage, and further, that the onset of the human autoantibody response may vary from several days to weeks, then in cases of suspected or known ductal injury, the clinical monitoring of antisperm antibody levels could enable testicular damage to be predicted prior to its development and thus be avoided.

Section: Discussionmentioning

confidence: 99%

Antisperm Autoantibody Response After Unilateral Vas Deferens Ligation in Rats: When Does it Develop?

CHEHVAL,

DOSHI,

KIDD

et al. 2002

Temporal Appearance of Antisperm Antibodies during Sexual Maturation of Rats after Obstruction of the Vas Deferens

FLICKINGER,

HERR,

BARAN

et al. 1995

The appearance of serum antisperm antibodies was studied during the maturation of rats in which the vas deferens was obstructed prepubertally. Vasa deferentia were ligated and divided bilaterally in 10‐day‐ old Lewis rats, while control animals received a sham operation at the same age. At ages between 14 and 128 days, blood samples were assayed for antisperm antibodies using an enzyme‐linked immunosorbent assay. There were no differences between obstructed and sham‐operated groups in mean antisperm antibodies from 14 through 56 days. However, in 91‐ and 128‐day‐ old rats mean antisperm antibody levels were much higher in obstructed than in control animals. This rise in antisperm antibodies occurred several weeks after the development of spermatids in the testes between 23 and 46 days. The presence of elevated antisperm antibodies in obstructed animals followed temporally the appearance of sperm throughout the lumen of the entire epididymis and the formation of spermatic granulomas. The results in this model suggest that consideration be given to repair of injured or obstructed vas deferens prior to puberty to forestall development of antisperm antibodies, as well as the formation of spermatic granulomas.

Epididymal Obstruction During Development Results in Antisperm Autoantibodies at Puberty in Rats

FLICKINGER,

BARAN,

HOWARDS

et al. 1998

An autoimmune response to sperm occurs after vasectomy, but there is little information on whether similar reactions occur after obstruction of the male reproductive tract at other points. Male Lewis rats received bilateral ligation of the corpus epididymidis or a sham operation at age 10 days, and the subsequent systemic antisperm autoantibody responses were compared to those observed following obstruction of the vas deferens. After sexual maturation, rats with epididymal ligations had antisperm antibodies on an enzyme‐linked immunosorbent assay that were significantly higher than those of sham‐operated animals and did not differ from antibody levels in vasectomized rats at the same ages. Western blot analysis showed that certain sperm proteins were recognized by antisperm antibodies after both epididymal ligation and vasectomy, including the previously identified “dominant” autoantigens at 73–83, 68–72, 48, 42, and 22 kDa. On the other hand, sera from rats with epididymal ligations recognized 60 and 52 kDa proteins that were not bound by most postvasectomy sera. Conversely, 42–48 and 38–42 kDa bands were more strongly and frequently stained after vasectomy than after epididymal ligation. The results demonstrate that antisperm antibodies are produced after obstruction of the epididymis and that the magnitude of the response is comparable to that after vasal obstruction. Differences in autoantigens recognized after epididymal and vasal obstructions may reflect maturational changes in sperm components that take place during the passage of spermatozoa through the epididymis.