Vas occlusion by styrene maleic anhydride (SMA), trade name RISUG (one of the promising male contraceptive procedures currently in phase III clinical trials), at 60 mg/vas deferens dissolved in 120 micro L dimethyl sulphoxide (DMSO) at up to a 540-day study period caused severe oligospermia in the first 2 to 3 ejaculations and uniform azoospermia in the subsequent ejaculations without toxicity in langur monkeys. The ejaculated spermatozoa were necroasthenoteratozoospermic, suggesting instant sterility. Routine hematology and clinical chemistry parameters and the serum testosterone and sperm antibody titers remained unchanged from their pretreatment values until 540 days vas occlusion. Histology of testes revealed continued spermatogenesis throughout the study period. The stages of spermatogenesis appeared normal until 300 days of vas occlusion. At 360 days of vas occlusion, germ cells appeared in the lumen. Degeneration of seminiferous epithelium was evident in some of the tubules. Following 420 days of vas occlusion, the central portion of the testis showed regressed seminiferous tubules depicting various shapes and devoid of germ cells, which continued until 540 days of vas occlusion. Ultrastructure of the testes after 540 days of vas occlusion revealed vacuolization in the cytoplasm of Sertoli cells and degenerative features in the membranes of the spermatocytes and spermatids in the affected seminiferous tubules. The sub-cellular features of the normal tubules were similar to those of controls. The results suggest focal degeneration of seminiferous epithelium in the central portion of the testis following long-term vas occlusion with SMA.
Antisperm antibodies (ASA) can cause infertility in both men and women. It is important to delineate the sperm antigens against which these ASA are directed. Sperm proteins were separated by 2D gel electrophoresis and transferred to nitrocellulose membrane and incubated with sera from fertile women or immunoinfertile women having ASA. The corresponding immunoreactive peptide spots were cored from the gel and analyzed by the two-dimensional (2D) gel electrophoresis/matrix-assisted laser desoprtion ionization-time of flight-mass spectrometry and liquid chromatography-mass spectrometry (MALDI-TOF-MS/LC-MS). A total of 68 spots belonging to 38 different proteins and their isomers were identified. Fourteen of these proteins and their isomers reacted with both the fertile and immunoinfertile sera. Twenty-four of these proteins reacted specifically only with the immunoinfertile sera and not with the fertile sera. Among them was a novel protein designated as a hypothetical protein FLJ32704 (accession # Q96MA6). An immunodominant sequence (amino acid 151-159) of this protein was identified and a nonamer peptide based upon this sequence (IQTLG1TPR) was synthesized and examined for its immunoreactivity. This synthetic peptide reacted with 90% (36/40) of immunoinfertile sera and not with any of the fertile sera (0/40) in the enzyme-linked immnosorbent assay (ELISA). In conclusion, using the 2D gel electrophoresis/MALDI-TOF-MS/LC-MS procedure, we have identified several known and at least one novel antigen against which the antibodies are present in sera of immunoinfertile but not fertile women. Some of these antigens may find applications in specific diagonsis and treatment of infertility/immunoinfertility, and in the development of new generation of contraceptive modalities including contraceptive vaccines.
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