IgG4-Related Disease with Selective Testicular Involvement- A Rare Entity: Case Report with Review of Literature.

Immunoglobin-G4 related disease (IgG4-RD) is an auto-immune inflammatory condition where patients present with a tumour-like mass that shows infiltration by plasma cell and subsequent fibrosis. It is a systemic condition that primarily involves the salivary glands, pancreas, kidneys, aorta, and retroperitoneum amongst other organs. Testicular involvement is a rare occurrence in this disease entity. A 55-year old male patient presented with the complaints of pain and swelling in the right scrotal region. Right-sided orchidectomy was carried out which on histopathology showed features suggestive of IgG4-RD which was later confirmed on immunohistochemistry. Whole body MRI revealed that no other organ was involved in the disease process in this patient. IgG4-RD has a variable clinical course and considerable overlap with its differentials. Imaging studies and serum IgG4 levels are neither confirmatory nor customarily diagnostic in every case. The only confirmatory diagnostic investigation is histopathological examination, which shows infiltration of IgG4+ plasma cells and fibrosis in the involved tissue. Whenever a mass-forming lesion with typical histomorphological features is encountered with involvement of multiple organs/anatomic sites, IgG4-related disease should be considered among the differentials, and clinicians of all disciplines should be familiar with this disease entity.

Recombinant Chimpanzee Adenovirus Vaccine AdC7-M/E Protects against Zika Virus Infection and Testis Damage.

The recent outbreak of Zika virus (ZIKV) has emerged as a global health concern. ZIKV can persist in human semen and be transmitted by sexual contact, as well as by mosquitoes, as seen for classical arboviruses. We along with others have previously demonstrated that ZIKV infection leads to testis damage and infertility in mouse models. So far, no prophylactics or therapeutics are available; therefore, vaccine development is urgently demanded. Recombinant chimpanzee adenovirus has been explored as the preferred vaccine vector for many pathogens due to the low preexisting immunity against the vector among the human population. Here, we developed a ZIKV vaccine based on recombinant chimpanzee adenovirus type 7 (AdC7) expressing ZIKV M/E glycoproteins. A single vaccination of AdC7-M/E was sufficient to elicit potent neutralizing antibodies and protective immunity against ZIKV in both immunocompetent and immunodeficient mice. Moreover, vaccinated mice rapidly developed neutralizing antibody with high titers within 1 week postvaccination, and the elicited antiserum could cross-neutralize heterologous ZIKV strains. Additionally, ZIKV M- and E-specific T cell responses were robustly induced by AdC7-M/E. Moreover, one-dose inoculation of AdC7-M/E conferred mouse sterilizing immunity to eliminate viremia and viral burden in tissues against ZIKV challenge. Further investigations showed that vaccination with AdC7-M/E completely protected against ZIKV-induced testicular damage. These data demonstrate that AdC7-M/E is highly effective and represents a promising vaccine candidate for ZIKV control.IMPORTANCE Zika virus (ZIKV) is a pathogenic flavivirus that causes severe clinical consequences, including congenital malformations in fetuses and Guillain-Barré syndrome in adults. Vaccine development is a high priority for ZIKV control. In this study, to avoid preexisting anti-vector immunity in humans, a rare serotype chimpanzee adenovirus (AdC7) expressing the ZIKV M/E glycoproteins was used for ZIKV vaccine development. Impressively, AdC7-M/E exhibited exceptional performance as a ZIKV vaccine, as follows: (i) protective efficacy by a single vaccination, (ii) rapid development of a robust humoral response, (iii) durable immune responses, (iv) robust T cell responses, and (v) sterilizing immunity achieved by a single vaccination. These advantages of AdC7-M/E strongly support its potential application as a promising ZIKV vaccine in the clinic.

IgG4-related disease of the paratestis in a patient with Wells syndrome: a case report.

BACKGROUND: We report a case of a 33-year-old man who presented with immunoglobulin (Ig)G4-related disease (IgG4-RD) forming a pseudotumor in the left paratesticular region during oral administration of corticosteroid for Wells syndrome, which involves cellulitis with eosinophilia. CASE PRESENTATION: The patient was introduced to our institution from a private hospital with a 3-month history of asymptomatic left scrotal mass. A 5-cm diameter nodule was palpable in the left scrotum. Tumor lesion in the left paratestis involving the epididymis and spermatic cord was observed on computed tomography and magnetic resonance imaging. Blood testing showed no abnormalities other than a minimal increase in C-reactive protein levels. Urine examination likewise revealed no significant findings. Left radical orchidectomy was performed under a diagnosis of left paratesticular neoplasm suspected as malignant tumor. The tumor was pathologically identified as IgG4-RD of the left paratestis involving the epididymis and spermatic cord. CONCLUSIONS: We present a first description of IgG4-RD in a patient with Wells syndrome and the ninth case of IgG4-RD in a scrotal organ, and discuss this very rare entity with reference to the literature. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_225.

Cadmium exposure increases susceptibility to testicular autoimmunity in mice.

Cadmium, one of various environmental toxicants, is known to suppress systemic immunity and to injure the testicular capillary endothelia with resultant necrosis of testicular tissues in mice and rats treated with high doses. Recently, it also became evident that cadmium can affect the integrity of the blood-testis barrier (BTB), the endocrine function of Leydig cells, apoptosis of germ cells and systemic immunity, even on treatment with a low dose that does not induce spermatogenic disturbance. Experimental autoimmune orchitis (EAO), i.e., an organ-specific autoimmunity of the testis, can be induced by repeated immunization with testicular antigens, and its pathology is characterized by lymphocytic inflammation and spermatogenic disturbance. In the present study, we investigated the morphological and functional changes of testes in mice treated with a low dose of cadmium chloride (CdCl2 ) and also examined its toxicity as to susceptibility to EAO. The results showed that exposure to 3 mg CdCl2 kg(-1) body weight did not affect the spermatogenic state. However, the BTB at the tubuli recti and the rete testis, but not the seminiferous tubules, was slightly weakened, and intra-testicular mRNA expression of interleukin (IL)-6, tumor necrosis factor-α and IL-1ß was significantly increased by the CdCl2 treatment. Furthermore, immunization with testicular antigens after the CdCl2 exposure significantly augmented the EAO severity. Therefore, exposure to a low dose of CdCl2 induces no significant disturbance of spermatogenesis, however, it does change the immunological microcircumstances in the testis, resulting in increased susceptibility to testicular autoimmunity.

IgG4-related paratesticular pseudotumor in a patient with autoimmune pancreatitis and retroperitoneal fibrosis: an extrapancreatic manifestation of IgG4-related disease.

In this report, we describe the first case of a patient with an IgG4-related paratesticular pseudotumor. He had histologically proven autoimmune pancreatitis, then later developed a scrotal mass. The orchiectomy specimen revealed that this was a paratesticular pseudotumor with histopathologic and immunohistochemistry findings characteristic of IgG4-related disease. Paratesticular pseudotumors are uncommon causes of intrascrotal masses and have an unexplained pathogenesis. A variety of genitourinary manifestations of IgG4-related disease including IgG4-related tubulointerstitial nephritis, IgG4-related ureteral pseudotumors, and IgG4-related prostatitis has been previously reported. The current case highlights the need to have a high index of suspicion for IgG4-tissue infiltration in patients with known autoimmune pancreatitis, particularly those with a pseudotumor.

Influence of inguinal hernia mesh repair on testicular flow and sperm autoimmunity.

BACKGROUND: The incidence of infertility caused by the mesh inguinal hernia repair is not known. The aim of this study was to determine circulation and immunological testicular disorders after inguinal hernia mesh repair which can be related with infertility. METHODS: From February 2010 to December 2010, 43 male patients who underwent inguinal hernia mesh repair were included in a prospective study. Testicular, capsular and intratesticular arterial flow dynamics were measured by Color Doppler ultrasound before the operation, in early and late postoperative period. The antisperm antibodies were analyzed before hernia repair and 5 months after. RESULTS: The difference between patients who underwent laparoscopic (Group I) and anterior open tension-free hernia repair (Group II) in age, duration of symptoms and hernia characteristics were not significant. Statistically significant differences were found in peak-systolic and end-diastolic velocity in testicular and intratesticular arteries in Group II and in peak-systolic velocity on all levels in Group I. Only Group I had significant differences in resistive index of intratesticular arteries. All the values returned to basal in late postoperative period except testicular peak-systolic velocity in Group I which stayed in normal range. Wilcox matched pair test showed significant difference between preoperative and late postoperative measurements of the antisperm antibodies only in Group II, but it was within normal range in all cases. CONCLUSIONS: Inguinal hernia mesh repair do not have clinically significant influence on testicular flow and immunological response.

The autoimmune bases of infertility and pregnancy loss.

Several lines of evidence suggest that autoimmune mechanisms may influence the reproductive life and fertility of both sexes, commonly manifesting as infertility or pregnancy loss. Part of the controversy that characterizes this assumption derives from the overlooked suspect of autoimmune conditions in the absence of symptoms or the limited physician awareness in a gynecological setting. Numerous autoimmune diseases, including but not limited to systemic lupus erythematosus and anti-phospholipid syndrome, may be associated with infertility and pregnancy loss through different putative mechanisms. First, serum autoantibodies such as anti-phospholipid, anti-thyroid, or antinuclear antibodies may be directly associated with infertility, regardless of the presence of a clinically overt autoimmune disease. Second, autoimmunity may affect all stages of fertility, via ovarian failure, testicular failure, implantation failure, and pregnancy loss. Third, infertility may also be secondary to vasculitis associated with other conditions such as systemic lupus erythematosus and diabetes mellitus. This review article will illustrate and critically discuss the available data on the link between the breakdown of tolerance that characterizes autoimmune diseases and the changes in reproductive life that affect patients in real clinical setting and that often constitute the iatrotropic stimulus.

Testicular ischemia due to intravascular large B-cell lymphoma: a novel presentation in an immunosuppressed individual.

A 56-year-old man presented with fever, disorientation, and testicular pain. He was receiving azathioprine immunosuppression for autoimmune hepatitis. Orchiectomy identified occlusion of spermatic cord vessels by intravascular large B-cell lymphoma (IVLBL) and ischemic changes in the testis. Tumor cells were positive for CD 10, CD 20, CD 30, and Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) and early region RNA (EBER). He was treated with the cessation of azathioprine, chemotherapy, anti-CD 20 immunotherapy, and radiotherapy. Twenty months after diagnosis, he is alive with no evidence of lymphoma or hepatitis. This is the first report of IVLBL presenting with testicular ischemia. It highlights the importance of prompt diagnosis and intervention to achieve durable response. That this lymphoma arose in the setting of immunosuppressive therapy introduces additional complexity relating to pathogenesis, clinical behavior, and treatment.

Pro-inflammatory cytokine response of the fluid contents of spermatoceles and epididymal cysts.

The aim of the study was to determine the cellular contents and concentrations of interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor alpha (TNF-alpha) in fluids of patients with spermatocele or epididymal cyst. Twenty-five symptomatic patients, 14 with epididymal cysts and 11 with spermatoceles, were included in the study. Fluids were obtained during surgical excision of the cysts and cytological smears were stained with May-Gruenwald-Giemsa to establish cell components. The concentrations of IL-6, IL-8 and TNF-alpha were measured by chemiluminescent immunometric assay. Cytological analysis of the fluids demonstrated various sperm forms ranging from immature germ cells to degenerated spermatozoa without inflammatory cells such as neutrophils and macrophages. The concentrations (mean+/- SEM, pg/mg protein) of IL-6, IL-8 and TNF-alpha were 13.52 +/- 1.40, 22.20 +/- 2.43, 3.51 +/- 1.43 in spermatocele fluids and 5.76 +/- 0.48, 11.57 +/- 1.89, 2.53 +/- 0.41 in epididymal cyst fluids. Both IL-6 and IL-8 concentrations in the spermatocele group were higher than in the epididymal cyst group (P < 0.0001). There were no differences in TNF-alpha concentrations between the groups (P > 0.05). These findings indicate that local production of pro-inflammatory cytokines is involved in cyst formation. The presence of immunologic activation in these fluids advocates a policy of selective surgical intervention in patients with spermatocele or epididymal cyst.

Major differences between the testis and epididymis in the induction of granulomas in response to extravasated germ cells. I. A light microscopical study in mice.

A spermatic granuloma is a chronic inflammatory lesion which surrounds extravasated spermatozoa. Clinically, the lesion develops in the interstitial spaces of the epididymis and vas deferens, and only exceptionally in the testis itself. In the present study, murine testes and epididymides were injured using a needle and the histological appearances of these organs was then compared. Traumatic injury induced extravasation of germ cells in both testes and epididymides. A few days later, spermatic granulomas consistently formed in the epididymides, however, such lesions were not induced in the testes. To examine the possibility that epididymal spermatozoa have inherently greater ability to form spermatic granulomas than do testicular germ cells, isolated epididymal spermatozoa or testicular germ cells were locally injected into the testes and epididymides of recipient mice. Spermatic granulomas readily formed in the epididymides after local injection of either epididymal spermatozoa or testicular germ cells. In contrast, such lesions did not form in the testes even when epididymal spermatozoa were injected. Therefore, this study suggests that the microenvironment of the testicular interstitium, rather than the extravasated components from the ruptured seminiferous tubules, is the main factor determining the limited formation of spermatic granulomas in the testis.

Lesions in the reproductive tract of boars experimentally infected with porcine rubulavirus.

"Blue eye" disease of pigs in Mexico is caused by porcine rubulavirus and characterized by infertility in sows and boars, nervous signs in young pigs, and corneal opacity in pigs of all ages. The pathogenesis of reproductive tract lesions in rubulavirus-infected boars has not previously been investigated. In a first experiment, four 9-month-old boars were inoculated with porcine rubulavirus and killed 5, 15, 30 or 45 days post-inoculation (pi). In a second experiment, four similar boars were inoculated with the same virus and two animals were killed on each of days 70 and 80 pi. Swelling of the head of the epididymis developed in all inoculated boars at approximately day 15 pi. Reduced spermatozoan motility and concentration were detected in semen samples collected from one boar from day 21 pi. At post-mortem examination, nodules were seen in the head of the epididymis of the boars killed 15, 30 or 45 days pi and the right testis of the pig killed 30 days pi was atrophic. Corresponding histopathological epididymal alterations included formation of spermatic granulomas and vacuolar degeneration of ductular epithelium. These lesions were associated with mononuclear cell infiltration and interstitial fibroplasia. Degeneration of seminiferous tubules and interstitial mononuclear cell infiltration were seen in the atrophic testis of the pig killed 30 days pi. There was fibrosis of the head of the epididymis in all boars killed 70 or 80 days pi and one of these animals also had right testicular atrophy associated with degeneration of seminiferous tubules, lymphocytic infiltration and giant cell formation. Porcine rubulavirus antigen was detected by immunofluorescence labelling in the head of the epididymis of the pigs killed 15, 30 or 45 days pi and in one animal killed on day 70 pi. These results indicate that porcine rubulavirus can cause severe epididymo-orchitis and reduced semen quality in sexually mature boars.

Specificity of antibodies directed against Env protein of human endogenous retroviruses in patients with germ cell tumors.

We report here that 85% of the patients with germ cell tumors (GCTs) produce antibodies directed against Env protein of human endogenous retroviruses. Individuals that received antitumor treatment showed a decrease with time in their antibody titers. Importantly, of the rare cases of non-GCT individuals with Env-antibodies (n= 15, 0.8%), none produced antibodies directed against the transmembrane domain (TM), whereas all tested Env-positive GCT patients (n= 49) generated such antibodies at high titers. TM is required for Env to be expressed at the cell surface. Thus, anti-TM antibodies constitute highly specific markers for GCT and may hint at a function of Env during tumorigenesis.

Scintigraphic diagnosis of syphilitic lesions in rabbits by radiolabelled monoclonal antibodies specific for Treponema pallidum.

Immunoscintigraphy with radiolabelled monoclonal antibodies has been widely used to detect solid tumours. The purpose of this study was to investigate its potential for the specific localization of syphilitic lesions. F(ab')2 fragments were prepared from murine monoclonal antibodies against Treponema pallidum produced in our laboratory and labelled with 131I. Bilateral testicular infections were created in rabbits by inoculation with T. pallidum or Staphylococcus aureus. Seven to 10 days after inoculation, radiolabelled antibodies were injected intravenously. Serial gamma images were then taken 2 h after the injection and at 24 h intervals thereafter. Beginning as early as 2 h post-injection, the testicles could be visualized with either specific or non-specific antibodies. Gamma images in the monoclonal antibody-treated, T. pallidum-infected group persisted up to 48 h post-injection. Lesions were not discernible from background in the S. aureus-infected group injected with the monoclonal antibody and the S. aureus-infected and T. pallidum-infected groups injected with the polyclonal antibody at 24 h post-injection or later. Therefore, due to its ability to differentiate between specific and non-specific antibody-generated images from 24 h post-injection, immunoscintigraphy using monoclonal antibodies specific for T. pallidum may be employed as one of the methods to diagnose difficult cases of syphilitic internal organ involvement as well as syphilis infection in seronegative HIV-infected patients.

Immuno-competent cells in the murine epididymis following infection with Escherichia coli.

Epididymitis was induced by retrograde injection of Escherichia coli into the vas deferens of 28 mice. A group of 28 saline-injected animals served as controls. On Days 1, 3, 7 and 28, groups of seven animals were killed. Bacterial culture was performed. Leucocyte numbers and distribution were determined in epididymides. In infected mice, E. coli were isolated from all epididymides on Days 1 and 3, but only from five of seven epididymides on Days 7 and 28. One week after infection, the total number of macrophages rose from about 10 to 28%. Significantly increased macrophage percentages were also found in animals killed 28 days after infection. A simultaneous increase in MHC class II positive cells was seen on Day 7. A total of 20% of the cells expressed MHC class II in infected epididymides (normal = 6%). A similar increase was found on Day 28 after infection. Most of the macrophages and MHC class II positive cells were located in the interstitium, fewer in the peritubular layer and nearly none in the epithelium. The main increase in these cells occurred in the interstitium and, to a lesser but significant extent, in the peritubular area. T-helper and T-suppressor/cytotoxic lymphocytes reached peak values on Day 28. The increase in T-lymphocytes and simultaneous appearance of plasma cells followed the increase in numbers of macrophages and MHC class II positive cells. They were located mainly in the interstitium. A sequential increase in leucocyte subsets and negative culture results for E. coli were observed on Days 7 and 28 (2/7 on each day). The inflammatory process was restricted to the interstitium.(ABSTRACT TRUNCATED AT 250 WORDS)

T and B lymphocyte subsets in spermatic granulomas in five rams.

Epididymal spermatic granulomas from five adult (greater than 4 years old) rams from a commercial flock were evaluated by quantitative histologic methods. Sections were stained for isotype specific immunoglobulin (Ig)-containing cells or specific lymphocyte subsets, as indicated by plasma membrane staining with monoclonal antibodies (MoAb). For the purpose of analysis, individual spermatic granulomas were allocated to one of three groups (early, resolving, or intermediate) on the basis of histologic examination. Ig-containing cells were most prevalent in early spermatic granulomas, and IgG-containing cells predominated in all spermatic granulomas regardless of their presumed age. IgM immunoglobulin-containing cells were the next in prevalence, and IgA-containing cells were infrequent. Assessment of lymphocyte subsets confirmed that lymphocytes present were of both T- and B-cell lineage and were well represented in all spermatic granulomas. CD4+ (MHC Class II-restricted "helper") T-cells were more prevalent in early spermatic granulomas than in intermediate or resolving types, while CD8+ (MHC Class I-restricted, "cytotoxic/suppressor") T-cells were more prevalent in spermatic granulomas of the intermediate type. These results suggest that in addition to an essentially foreign body reaction to extravasated spermatozoa, both local production of antibody and accumulation of a variety of B- and T-lymphocytes are present in ovine spermatic granulomas.

The response of the regional lymph node to epididymal sperm granulomas after vasectomy.

The cause of the variable immune response in the regional testicular lymph node of inbred Albino Swiss rats after vasectomy was investigated in two experiments. In the first, the ductus deferens was transected at its junction with the epididymis so that, in every case, sperm granulomas developed in the epididymis, from which lymph is known to drain invariably to the testicular node. In spite of this, not all testicular nodes showed histological signs of an immune response at 12 weeks after vasectomy. In the second experiment the contents of epididymal lymphatics were compared in vasectomised rats and sham-operated controls at intervals of up to 18 months after operation. Lymphatics in animals with an 'active' epididymal granuloma invariably contained numbers of macrophages and lymphocytes, thought to be involved in antigen transport, while those of controls contained none. It is concluded that variations in the lymphatic drainage of vasal granulomas were not primarily responsible for the variable lymph node response to vasectomy previously reported.

PIP: 2 experiments involving inbred Albino Swiss rats after vasectomy suggest that variations in the lymphatic drainage of sperm granulomas are not, as previously suggested, a major factor in the variability of the regional testicular lymph node's response to this procedure. More significant to the antigenic stimulation of the node seems to be leukocytes released from sperm granulomas. In the 1st experiment, the ductus deferens was divided at its junction with the epididymal duct and sperm granulomas were induced to form in the cauda, which drains into the testicular node. The resultant testicular nodes exhibited a range of weights and cortical nodule content and 1 experimental node was indistinguishable from control nodes. The presence of an epididymal granuloma did not inevitably lead to an immune response in the regional node; spermatozoa were relatively numerous in the node of only 1 of 8 experimental rats. In the 2nd experiment, the intrinsic lymphatics of the epididymis in rats with epididymal granulomas after vasectomy were compared with those in sham-operated controls. Lymphatics in the epididymis adjacent to the granuloma in vasectomized rats contained numerous macrophages and lymphocytes--findings that were not recorded in control animals or vasectomized rats in which a granuloma had not developed. The abundance of macrophages and lymphocytes adjacent to (a granuloma suggests that these cells came from the granuloma and are most likely active agents in antigen transport from granuloma to node.

Testicular obstruction: clinicopathological studies.

Genital tract reconstruction has been attempted in subfertile men with obstructive azoospermia (370 patients) or unilateral testicular obstruction (80 patients), and in vasectomised men undergoing reversal for the first (130 patients) or subsequent (32 patients) time. Histopathological changes in the obstructed testes and epididymes, and immunological responses to the sequestered spermatozoa have been studied to gain insight into possible causes of failure of surgical treatment. The results of surgery have been assessed by follow-up sperm counts and occurrence of pregnancies in the female partners. The best results were obtained with vasectomy reversal (patency 90%, pregnancy 45%), even after failed previous attempts (patency 87%, pregnancy 37%). Epididymovasostomy gave good results with postinfective caudal blocks (patency 52%, pregnancy 38%), while postinfective vasal blocks were better corrected by total anatomical reconstruction (patency 73%, pregnancy 27%) than by transvasovasostomy (patency 9%, no pregnancies). Poor results were obtained with capital blocks (patency 12%, pregnancy 3%), in which substantial lipid accumulation was demonstrated in the ductuli efferentes; three-quarters of these patients had sinusitis, bronchitis or bronchiectasis (Young's syndrome). There is circumstantial evidence to suggest that this syndrome may be a late complication of mercury intoxication in childhood. After successful reconstruction, fertility was relatively reduced in those men who had antibodies to spermatozoa, particularly amongst the postinfective cases. Similarly, impaired fertility was found in men with unilateral testicular obstruction and antibodies to spermatozoa. Mononuclear cell infiltration of seminiferous tubules and rete testis was noted occasionally, supporting a diagnosis of autoimmune orchitis; although rare, this was an important observation as the sperm output became normal with adjuvant prednisolone therapy.

Presence and distribution of leucocyte subsets in the murine epididymis after vasectomy.

Male mice were vasectomized by 'open-ended' or 'closed' techniques. After 4 weeks the cell-mediated immune reactions were compared with those of sham-operated animals by immunohistochemical localization of leucocytes, using specific monoclonal antibodies. Macrophages and MHC class II antigen-positive cells were the major cell types to appear in all regions of the epididymis after both types of operation. There was recruitment of T-helper/inducer leucocytes but not of T-suppressor-cytotoxic cells. An increased presentation of macrophage-migration inhibiting factor antigen appeared in interstitial and peritubular locations. After 'closed' and 'open-ended' vasectomy granulomata developed in the epididymis. The sperm-containing lumen of these granulomata was invaded by macrophages, MHC class II-positive cells and T-helper/inducer lymphocytes. This mouse model thus reveals a significant epididymal inflammatory response of the epididymis to vasectomy.

Spermatogenic disturbance induced in mice by combined local injection of monoclonal antibodies to Sertoli cell and to basal lamina of seminiferous tubule.

Two kinds of hybridoma clones, one producing monoclonal antibodies against Sertoli cell (TM-1) and the other the basal lamina of the seminiferous tubule (TM-2), were raised by fusion between P3X63Ag8-653 mouse myeloma cells and spleen cells of BALB/c mice (H-2d) immunized with testicular homogenate of the same inbred mice. Immunohistochemically, TM-1 reacted specifically with cytoplasmic component of Sertoli cell and TM-2 with basal lamina of the seminiferous tubule. Using these monoclonal antibodies, spermatogenic disturbance was induced experimentally in BDF1 (H-2b/d) by intratesticular injection of a set of these two antibodies. Single injection of either TM-1 or TM-2 failed to induce the lesion. This fact indicated that TM-1 antibody could reach the Sertoli cell to impair its function, which was otherwise inaccessible without coincidental action of TM-2 antibody. TM-2 antibody appeared to alter the permeability of the basal lamina of the tubule and lower its barrier effect.

The effect of testicular torsion on contralateral testis and the production of antisperm antibodies in rabbits.

It has been previously shown that unilateral testis torsion can cause disruptive anatomic changes in the contralateral testis of rats. This study was conducted to duplicate these findings in rabbits and analyze their serum for the production of the immunoglobulin G class of antisperm antibodies and determine whether the proposed immune response demonstrated by contralateral anatomic testis changes was mediated by these antibodies. New Zealand white rabbits were divided into 8 groups. One had a sham operation, 1 had testis biopsy, 3 groups had ligation of the right testicular vessels with subsequent orchiectomy in 2 groups at 36 and 72 hours, and 3 groups had 720-degree torsion of the right testis. Half of the animals were sacrificed after 4 weeks and the other half after 8 weeks. Contralateral histology was analyzed in all rabbits and only those with torsion showed abnormal tubular architecture and defective spermatogenesis. Detorsion at 36 hours and 96 hours did not protect against contralateral testis damage. No animal whose vessels were ligated, no matter what treatment protocol was employed, showed contralateral damage. All rabbit sera were tested for the presence of immunoglobulin G antiserum antibodies against a control rabbit that was a known antibody former, using an enzyme-linked immunosorbent technique. No experimental animal had detectable levels of antisperm immunoglobulin G when compared to controls. Three male rabbits who were converted to antisperm antibody formers by injection of sperm did not show anatomic changes in their testes.