In a benchmark study, Isojima and colleagues established H6-3C4, the first successful heterohybridoma immortalized from the peripheral blood lymphocytes of an infertile woman who exhibited high sperm-immobilizing antibody titers. The present report demonstrates the identity between the glycoprotein antigens recognized by the human H6-3C4 monoclonal antibody (mAb) and the murine S19 mAb, generated in our laboratory to sperm agglutination antigen-1 (SAGA-1). Both mAb's recognize N-linked carbohydrate epitopes on the 15-25 kDa, polymorphic SAGA-1 glycoprotein that is localized to all domains of the human sperm surface. Treatment with phosphatidylinositol-specific phospholipase C demonstrated that SAGA-1 is anchored in the sperm plasmalemma via a GPI-lipid linkage. Immunoaffinity purification and microsequencing indicated that the core peptide of the SAGA-1 glycoprotein is identical to the sequence of CD52, a GPI-anchored lymphocyte differentiation marker implicated in signal transduction. Comparison of anti-SAGA-1 and anti-CD52 immunoreactivities revealed that the sperm form of CD52 exhibits N-linked glycan epitopes, including the epitope recognized by the infertility-associated H6-3C4 mAb, which are not detected on lymphocyte CD52. Thus, the two populations of the CD52 glycoprotein on lymphocytes and spermatozoa represent glycoforms, glycoprotein isoforms with the same core amino acid sequence but different carbohydrate structures. Furthermore, mAb's to the unique carbohydrate epitopes on sperm CD52 have multiple inhibitory effects on sperm function, including a cytotoxic effect on spermatozoa in the presence of complement. These results are the first to implicate unique carbohydrate moieties of a sperm CD52 glycoform as target epitopes in the anti-sperm immune response of an infertile woman. Furthermore, localization of CD52 on all domains of the sperm surface coupled with the multiple sperm-inhibitory effects of antibodies to its unique carbohydrate moieties suggest opportunities for immunocontraceptive development.
The occurrence of spermatic granulomas of the vas deferens was studied in Lewis rats at intervals up to 7 months after vasectomy or vasectomy followed 3 months later by vasovasostomy. The incidence of granuloma progressed with time to involve one or both tracts in 100% of vasectomized rats. In addition, the majority of animals developed new granulomas after vasovasostomy, even though fluid flow through the reconnected vas deferens was demonstrated in vitro. When individual tracts were analyzed, the weight of the testis was related to ipsilateral spermatic granuloma formation in both vasectomy and vasovasostomy groups at 3 and 4 months after initial operation. Testes were small in the absence of a granuloma but similar to those of sham‐operated rats if a granuloma was present. The possible protective effect of spermatic granuloma formation on the testis is discussed.
The occurrence of alterations in testicular weight and morphology after vasectomy and vasectomy reversal by vasovasostomy was studied in Lewis rats. Animals were studied 3, 4, and 7 months after bilateral vasectomy or a vasectomy followed 3 months later by vasovasostomy. Other rats served as sham-operated controls. The weights of the testes in vasectomy and vasovasostomy animals fell into two groups-small testes weighing less than 0.88 g and normal-sized testes of 1.2 g or more. When the extent of testicular alterations was estimated in sections for light microscopy by use of a semiquantitative testicular biopsy score count (TBSC), the morphology of the testes corresponded closely to the testis weight (r = .94), small testes having correspondingly low TBSC scores. In severely altered small testes, the seminiferous tubules were narrower than in sham-operated rats, and numbers of germ cells were greatly depleted. Many tubules contained only Sertoli cells and spermatogonia, although spermatocytes were present in a minority of tubules. A few seminiferous tubules contained multinucleate spermatids. Electron microscopy of severely altered tubules revealed closely apposed processes of Sertoli cells, which contained filaments, microtubules, and endoplasmic reticulum. In contrast, testes with normal weight in vasectomy and vasovasostomy groups resembled those of the sham-operated animals. Comparison of distributions of testicular biopsy score counts demonstrated differences between vasectomy and vasovasostomy groups as time after operation increased. At the 3-4-month intervals, approximately one-third of the testes were severely altered in both vasectomy and vasovasostomy groups.(ABSTRACT TRUNCATED AT 250 WORDS)
An indirect enzyme-linked immunosorbent assay (ELISA) was employed to monitor antisperm autoantibodies in 16 Lewis rats for up to 36 weeks following vasectomy. This assay was capable of discriminating all prevasectomy from postvasectomy sera at a 1:16 dilution. Weekly serum samples were obtained for the first 13 weeks and bimonthly samples thereafter. Half of the animals developed a positive antisperm autoantibody response by the end of the first postoperative week. By the end of the second week, 81% of the animals had positive responses. The greatest proportion (88%) of animals having a positive response over the course of the study was found at the end of the seventh postoperative week and the highest mean absorbance value for all 16 animals was observed at this time. Only 25% of the animals had positive responses for antisperm autoantibody at the end of the 35th week of the study. These findings indicate that circulating antisperm autoantibodies arise in the Lewis rat earlier than has been generally appreciated. The time course is similar to that of antibody titers to infectious agents or arising from inoculation of rats with spermatozoa. These findings on autoantibody levels in the Lewis rat are compared with the dynamics of antisperm autoantibody formation in man.
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