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Basic and Clinical Andrology 2017Options for male contraception are limited. The purpose of this study was to use a nonhuman primate model to evaluate Vasalgel™, a high molecular weight polymer being...
BACKGROUND
Options for male contraception are limited. The purpose of this study was to use a nonhuman primate model to evaluate Vasalgel™, a high molecular weight polymer being developed as a contraceptive device for men.
METHODS
Sixteen adult male rhesus monkeys received intravas injections of Vasalgel, consisting of 25% styrene maleic acid in dimethyl sulfoxide. After a one-week recovery, males were returned to outdoor group housing, which included at least 3 and up to 9 intact, breeding females with a successful reproductive history.
RESULTS
Treated males have had no conceptions since Vasalgel injections. All males were housed with intact females for at least one breeding season and seven have been almost continually housed with females for 2 years. Complications were minor and included one incident of incorrect placement of Vasalgel into the vas deferens and the development of a sperm granuloma in one animal. Three unilateral vasectomies were performed, one was necessary for incorrect placement of Vasalgel, the other two were elective.
CONCLUSIONS
Intravas injection of Vasalgel in sexually mature adult male rhesus monkeys was effective in preventing conception in a free-living, group environment. Complications were few and similar to those associated with traditional vasectomy.
PubMed: 28191316
DOI: 10.1186/s12610-017-0048-9 -
Fertility and Sterility Apr 1978
Topics: Genital Diseases, Male; Granuloma; Humans; Male; Spermatozoa; Vas Deferens; Vasectomy
PubMed: 648655
DOI: No ID Found -
Molecular Reproduction and Development Jun 2010SED1/MFG-E8, herein referred to as SED1, is a bimotif adhesive protein with ascribed functions in a range of cell-cell interactions, including sperm-egg binding. In the...
SED1/MFG-E8, herein referred to as SED1, is a bimotif adhesive protein with ascribed functions in a range of cell-cell interactions, including sperm-egg binding. In the male reproductive tract, SED1 is secreted by the initial segment of the epididymis, where it coats sperm and subsequently facilitates binding to the egg zona pellucida. We have recently reported that SED1-null epididymides show an unexpected incidence of spermatic granulomas, reflecting breakdown of the epithelium and a consequent autoimmune response against sperm antigens. However, spermatic granulomas are most often manifest in the distal segments of the epididymis, whereas the bulk of SED1 is expressed in the proximal epididymis. In some models, the presence of granulomas in the distal epididymis is associated with an underlying defect in the maintenance of luminal fluid homeostasis. Herein, we report that SED1-null epididymal fluid is both hypo-osmotic and alkaline, relative to wildtype epididymal fluid. Furthermore, the SED1-null epididymal epithelium exhibits various hallmarks of disrupted fluid reabsorption and pH regulation, including altered morphology of clear cells, increased intracellular vesicles, and apical distribution of VATPase. Results indicate that the SED1-null epididymal pathologies are not the secondary consequences of defective testes or efferent ducts or of improper epididymal differentiation, unlike that seen in other epididymal models. The expression and distribution of various ion exchangers, channels, and enzymes that mediate fluid transport and pH regulation are examined in wildtype and SED1-null epididymides, and models to account for how SED1 functions in luminal fluid dynamics are discussed.
Topics: Animals; Body Fluids; Epididymis; Epithelial Cells; Hydrogen-Ion Concentration; Male; Membrane Proteins; Mice; Mice, Knockout; Osmolar Concentration
PubMed: 20422713
DOI: 10.1002/mrd.21189 -
Proceedings of the National Academy of... May 2011Vasectomy is a well accepted global contraceptive approach frequently associated with epididymal granuloma and sperm autoantibody formation. To understand the long-term...
Vasectomy is a well accepted global contraceptive approach frequently associated with epididymal granuloma and sperm autoantibody formation. To understand the long-term sequelae of vasectomy, we investigated the early immune response in vasectomized mice. Vasectomy leads to rapid epithelial cell apoptosis and necrosis, persistent inflammation, and sperm granuloma formation in the epididymis. Vasectomized B6AF1 mice did not mount autoimmune response but instead developed sperm antigen-specific tolerance, documented as resistance to immunization-induced experimental autoimmune orchitis (EAO) but not experimental autoimmune encephalomyelitis. Strikingly, tolerance switches over to pathologic autoimmune state following concomitant CD4(+)CD25(+)Foxp3(+) regulatory T cell (Treg) depletion: unilaterally vasectomized mice produce dominant autoantibodies to an orchitogenic antigen (zonadhesin), and develop CD4 T-cell- and antibody-dependent bilateral autoimmune orchitis. Therefore, (i) Treg normally prevents spontaneous organ-specific autoimmunity induction by persistent endogenous danger signal, and (ii) autoantigenic stimulation with sterile autoinflammation can lead to tolerance. Finally, postvasectomy tolerance occurs in B6AF1, C57BL/6, and A/J strains. However, C57BL/6 mice resisted EAO after 60% Treg depletion, but developed EAO after 97% Treg reduction. Therefore, variance in intrinsic Treg function--a possible genetic trait--can influence the divergent tolerogenic versus autoimmune response to vasectomy.
Topics: Animals; Autoantibodies; Autoimmunity; Blotting, Western; Cell Proliferation; Electrophoresis, Polyacrylamide Gel; Immune Tolerance; Male; Membrane Proteins; Mice; Mice, Mutant Strains; Spermatozoa; Statistics, Nonparametric; T-Lymphocytes, Regulatory; Vasectomy
PubMed: 21502500
DOI: 10.1073/pnas.1017615108 -
Asian Journal of Andrology Jan 2013This study is to evaluate the effectiveness of a modified single-armed suture technique for microsurgical vasoepididymostomy (VE) in patients with epididymal obstructive...
This study is to evaluate the effectiveness of a modified single-armed suture technique for microsurgical vasoepididymostomy (VE) in patients with epididymal obstructive azoospermia. From September 2011 to December 2011, microsurgical two-suture longitudinal intussusception VEs were performed using our modified single-armed suture technique in 17 men with epididymal obstructive azoospermia at our hospital. Two of these patients underwent repeated VEs after previous failed VEs, and one patient underwent unilateral VE because of an occlusion of the left abdominal vas deferens. The presence of sperm in the semen sample at 3 months postoperation was used as the preliminary endpoint of this study. Each patient provided at least one semen sample at the 3-month time point, and the patency was assessed by the reappearance of sperm (>10(4) ml(-1)) in the semen. The mean operative time for the modified technique was 219 min. Patency was noted in 10 men (58.8%), including one patient who underwent repeated VE. The patient who underwent unilateral anastomosis manifested no sperm postoperatively in his semen. Sperm granulomas were not detected in this cohort. The results of this study demonstrate that our modified technique for microsurgical longitudinal intussusception VE is effective. We believe that it is a practical alternative that may reduce operation time and obviate the suture crossing.
Topics: Adult; Anastomosis, Surgical; Azoospermia; Epididymis; Humans; Male; Microsurgery; Semen Analysis; Sperm Count; Suture Techniques; Sutures; Treatment Outcome; Urologic Surgical Procedures; Vas Deferens
PubMed: 23042447
DOI: 10.1038/aja.2012.100 -
Fertility and Sterility Feb 1978
Review
Topics: Animals; Antibodies; Epididymis; Female; Fertility; Granuloma; Humans; Male; Microsurgery; Pregnancy; Prospective Studies; Sperm Transport; Spermatogenesis; Spermatozoa; Sterilization Reversal; Testis; Vasectomy
PubMed: 342283
DOI: 10.1016/s0015-0282(16)43088-8 -
PloS One 2016Phospholipase Cγ2 (PLCγ2)-deficient mice exhibit misconnections of blood and lymphatic vessels, and male infertility. However, the cell type responsible for vascular...
Phospholipase Cγ2 (PLCγ2)-deficient mice exhibit misconnections of blood and lymphatic vessels, and male infertility. However, the cell type responsible for vascular partitioning and the mechanism for male infertility remain unknown. Accordingly, we generated a mouse line that conditionally expresses endogenous Plcg2 in a Cre/loxP recombination-dependent manner, and found that Tie2-Cre- or Pf4-Cre-driven reactivation of Plcg2 rescues PLCγ2-deficient mice from the vascular phenotype. By contrast, male mice rescued from the vascular phenotype exhibited epididymal sperm granulomas. As judged from immunostaining, PLCγ2 was expressed in clear cells in the epididymis. PLCγ2 deficiency did not compromise differentiation of epididymal epithelial cells, including clear cells, and tube formation at postnatal week 2. However, luminal expansion of the epididymal duct was impaired during the prepubertal period, regardless of epithelial cell polarity and tube architecture. These results suggest that PLCγ2-deficient clear cells cause impaired luminal expansion, stenosis of the epididymal duct, attenuation of luminal flow, and subsequent sperm granulomas. Clear cell-mediated luminal expansion is also supported by the observation that PLCγ2-deficient males were rescued from infertility by epididymal epithelium-specific reactivation of Plcg2, although the edematous and hemorrhagic phenotype associated with PLCγ2 deficiency also caused spontaneous epididymal sperm granulomas in aging males. Collectively, our findings demonstrate that PLCγ2 in clear cells plays an essential role in luminal expansion of the epididymis during the prepubertal period in mice, and reveal an unexpected link between PLCγ2, clear cells, and epididymal development.
Topics: Animals; Epididymis; Gene Expression Regulation, Developmental; Genetic Engineering; Granuloma; Hemorrhage; Lymphatic Vessels; Male; Mice; Phospholipase C gamma; Recombination, Genetic
PubMed: 26950550
DOI: 10.1371/journal.pone.0150521 -
Monocytic orchitis and aspermatogenesis in normal and vasectomized rhesus macaques (Macaca mulatta).The American Journal of Pathology Oct 1980The immunopathologic findings in the testes and kidneys of 25 long-term vasectomized monkeys and of 13 age-matched control animals were compared. Antisperm antibody was...
The immunopathologic findings in the testes and kidneys of 25 long-term vasectomized monkeys and of 13 age-matched control animals were compared. Antisperm antibody was found in serum samples from 60% of vasectomized monkeys and in no samples from control animals. Orchitis, aspermatogenesis, or both, resembling allergic orchitis, was noted in 92% of vasectomized animals and in 23% of controls. Epididymitis and epididymal granuloma occurred exclusively in the vasectomized animals (52%). By immunofluorescence, granular deposits of IgA, IgG, and/or C3 in the basal lamina of the ductuli efferentes and the caput epididymidis were detected in 45% of the control monkeys. In vasectomized animals, the incidence of immune deposits increased to 91%, and the deposits became more widespread. Although both vasectomized and control animals had IgM, IgG, or both, in the glomerular mesangial region, C3 was found in vasectomized monkeys only (29%). The results of this study indicate that monocytic infiltrations with aspermatogenesis in association with immune deposits along the excurrent duct normally occur in subhuman primates, and that these changes increase in incidence after vasectomy. Although the testicular disease highly resembles allergic orchitis, an immunologic basis remains to be established.
Topics: Animals; Autoantibodies; Epididymitis; Kidney; Macaca mulatta; Male; Orchitis; Spermatocytes; Spermatogenesis; Testis; Vasectomy
PubMed: 7446699
DOI: No ID Found -
Journal of Anatomy Aug 2004Using stereological methods, especially the optical disector for unbiased estimation of nuclear number, our recent study demonstrated that long-term (6 or 12 months)...
Using stereological methods, especially the optical disector for unbiased estimation of nuclear number, our recent study demonstrated that long-term (6 or 12 months) vasectomy in the rhesus monkey had no significant effects on spermatogenesis (Peng et al. Reproduction 2002, 124, 847-856). This study aimed to determine the scenario in the rabbit using the same morphometric methodology. Three groups of normal male Japanese white rabbits (aged 4-5 months) were subjected to unilateral vasectomy; 10 days, 6 months and 12 months later both testes and epididymides were removed. Testicular and epididymal methacrylate-embedded sections were obtained for stereology. Vasectomy-induced damage to spermatogenesis was observed, primarily sloughing of spermatogenic cells with a greater reduction in the number of advanced (adluminal) cells. The damage was most severe at 10 days, occurring in all the testes on the vasectomized side and involving sloughing of even type A spermatogonia, the number of which returned to normal at 6 and 12 months. Damage was less severe at 6 and 12 months, being found in half of the testes of the vasectomy side, in which the total numbers of later germ cell types were 24.0-59.1% (spermatocytes) and 0.3-11.6% (spermatids) of control at 6 months, and 20.1-22.1% (spermatocytes) and 0.4-12.0% (spermatids) of control at 12 months. By contrast, Sertoli cell number per testis was unchanged following vasectomy in any group. Epididymis on the vasectomy side, especially at 10 days and 6 months, appeared larger than on the contralateral side, but this difference was not statistically significant, and no sperm granuloma was seen in the epididymis.
Topics: Animals; Cell Count; Epididymis; Male; Rabbits; Seminiferous Tubules; Spermatocytes; Spermatogenesis; Spermatozoa; Testis; Time Factors; Vasectomy
PubMed: 15291797
DOI: 10.1111/j.0021-8782.2004.00322.x -
Journal of Clinical Pathology Apr 1988To establish the prevalence of vasitis nodosa in patients who had undergone vasectomy segments of vas deferens resected from 40 patients at the time of vasectomy...
To establish the prevalence of vasitis nodosa in patients who had undergone vasectomy segments of vas deferens resected from 40 patients at the time of vasectomy reversal were examined histologically and immunohistochemically. The findings were correlated with clinical history and postoperative outcome. Controls comprised segments of normal vas deferens excised at vasectomy. Twenty of the 40 vasovasostomy specimens showed vasitis nodosa; in 13 this was associated with sperm granulomas and in two with spermatocoeles. The vasitis nodosa was characterised by multiple small ductules extending from the central lumen of the vas into the muscle layers and adventitia. In 14 cases there was mucinous metaplasia of the epithelium lining the ductules. The number of nerve fibres in the submucosa and muscle layers was reduced after vasectomy. In patients with vasitis, however, hyperplasia of nerve fibres in the adventitia (16 of 20 cases) and formation of neuromas were seen. Nerve fibre hyperplasia was seen in only one, and sperm granulomas and spermatocoeles in none of the 20 specimens without vasitis nodosa. The development of vasitis nodosa was independent of the patients' age or the interval between vasectomy and reversal. The restoration of fertility did not seem to be affected by previous vasitis nodosa.
Topics: Adult; Age Factors; Genital Diseases, Male; Granuloma; Humans; Male; Middle Aged; Postoperative Complications; Sperm Count; Sterilization Reversal; Testis; Vas Deferens; Vasectomy
PubMed: 3366928
DOI: 10.1136/jcp.41.4.419