Immunodeviation towards T cell-mediated immune response in the testes of LPS-induced mouse epididymo-orchitis.

The testicular consequences of acute epididymo-orchitis remain largely unelucidated in long-term damage, which might be a neglected factor for male infertility. In this study, the differential phenotype of testicular immune cell subpopulations in lipopolysaccharide (LPS)-induced mouse epididymo-orchitis were analyzed by flow cytometry on day 1, day 7, and day 28. The number of macrophages, neutrophils, and myeloid-derived suppressor cells (MDSCs) steadily decreased in the testes with inoculation. Total F4/80-CD11c+ dendritic cells (DCs) maintained a relatively stable level, whereas conventional type 1 dendritic cells (cDC1) increased gradually from day 1 to day 28. There was a lower number of CD4+ and CD8+ T cells at day 1 and day 7, and they had similar results with a ceiling level at day 28. The testes displayed a higher level of CD3+ T cells but a lower frequency of macrophages, cDC2, and neutrophils at 28 days post-inoculation compared with the epididymis. In summary, our data indicates acute epididymo-orchitis could lead to long-term damage in the testes, which is characterized by CD3+ T cell (including CD4+ and CD8+ T cells)-mediated immune responses.

Investigation of Serum Human Epididymitis Protein 4 Level in Rats with Experimental Acute Pancreatitis.

BACKGORUND: We aimed to show whether the serum level of Human Epididymitis Protein 4 increases in rats with an experimental acute pancreatitis model created by cerulein. METHODS: This study included 24 male Sprague-Dawley rats which were randomly divided into 4 groups each containing 6 rats. CONTROL: the group treated with saline, Group 1: pancreatitis group created with cerulein at a total dose of 80 µg/kg, Group 2: pancreatitis group created with cerulein at a total dose of 120 µg/kg, Group 3: pancreatitis group created with cerulein at a total dose of 160 µg/kg. RESULTS: There were statistically significant differences between edema, acinar necrosis, fat necrosis, and perivascular inflammation scores among the study groups. While the degree of all histopathological findings is lowest in the control group, pancreatic parenchyma damage increases as the amount of injected cerulein increases. There was no statistically significant difference between alanine aminotransferase, aspartate aminotransferase, and Human Epididymis Protein 4 values between study groups. On the other hand, there was a statistically significant difference between amylase and lipase values. The lipase value of the control group was significantly lower than the lipase value of the second and third groups. The amylase value of the control group was significantly lower than all other groups. The highest Human Epididymis Protein 4 value was measured as 104 pmol/L in the first pancreatitis group, where the severity of pancreatitis was mild. CONCLUSIONS: In the present study, it was concluded that the Human Epididymis Protein 4 value increased in the case of mild pancreatitis, but there is no correlation between the severity of pancreatitis and the Human Epididymis Protein 4 value.

Case Report: Dendritic Cells and Macrophages Capture Sperm in Chronically Inflamed Human Epididymis.

Chronic inflammation of the male genital tract is thought to be a primary etiological factor of male infertility. The abundance and activation of macrophages and dendritic cells in patients with chronic inflammation of genital tract were closely associated with oligozoospermia and asthenospermia. Chronic epididymitis appears to be more important than seminal vesiculitis or prostatitis due to the direct interaction between spermatozoa and epididymal inflammatory cells. In this study, we present a case report of a 41-year-old male with oligoasthenospermia and chronic epididymitis. Hematoxylin-eosin staining and immunofluorescence analyses showed that antigen presenting cells including macrophages and dendritic cells were found capturing spermatozoa in the lumen of cauda epididymis. To our knowledge, this is the first case report that directly observed dendritic cells capturing spermatozoa in the lumen of an inflamed epididymis. This finding directly explains chronic epididymitis as the possible cause of oligospermia in patients.

A case report: Actinobaculum suis infection associated with formation of pyogranuloma, epididymitis and azoospermia in a boar.

BACKGROUND: Actinobaculum suis is a bacterium known to cause infections of the urogenital tract of sows. Infection can occur through close contact to boars, who frequently carry the pathogen in their preputial diverticulum but do not become clinically diseased themselves. In the current case, Actinobaculum suis was isolated from pyogranuloma of inflamed epididymis in a boar with poor fertility. CASE PRESENTATION: Increased return to oestrus rate, which worsened after the purchase of a new boar, was reported in an organic farm in Switzerland. During herd examination, azoospermia of the boar was diagnosed, and slaughter, followed by examination of its urogenital tract, was carried out. Pathologically, pyogranuloma formation and epididymitis were diagnosed. Bacteriology of the pyogranulomas showed growth of Actinobaculum suis and mixed flora. After the boar was replaced, the return to oestrus rate improved tremendously. CONCLUSION: A close relative of Actinobaculum suis, namely Actinotignum schaalii, has already been associated with epididymitis in humans. Considering the present case and the parallels in human medicine, Actinobaculum suis should be included in the list of differentials of boars with poor fertility.

Differential Immune Response to Infection and Acute Inflammation Along the Epididymis.

The epididymis is a tubular structure connecting the vas deferens to the testis. This organ consists of three main regions-caput, corpus, and cauda-that face opposing immunological tasks. A means of combating invading pathogens is required in the distally located cauda, where there is a risk of ascending bacterial infections originating from the urethra. Meanwhile, immune tolerance is necessary at the caput, where spermatozoa with immunogenic neo-antigens originate from the testis. Consistently, when challenged with live bacteria or inflammatory stimuli, the cauda elicits a much stronger immune response and inflammatory-inflicted damage than the caput. At the cellular level, a role for diverse and strategically positioned mononuclear phagocytes is emerging. At the mechanistic level, differential expression of immunoprotective and immunomodulatory mediators has been detected between the three main regions of the epididymis. In this review, we summarize the current state of knowledge about region-specific immunological characteristics and unveil possible underlying mechanisms on cellular and molecular levels. Improved understanding of the different immunological microenvironments is the basis for an improved therapy and counseling of patients with epididymal infections.

Increase of leucocyte-derived extracellular traps (ETs) in semen samples from human acute epididymitis patients-a pilot study.

PURPOSE: To study the effector mechanism against pathogens of polymorphonuclear neutrophils (PMN) and macrophages, called ETosis, involving the release of extracellular traps (ETs) in patients with acute epididymitis. To assess the different ET phenotypes present in semen samples and to identify correlations between ETosis and clinical parameters. MATERIALS AND METHODS: Samples from patients diagnosed with acute epididymitis were examined and compared with samples from uninfected controls. Biochemical analyses of seminal fluid included determination of peroxidase, α-glucosidase, fructose, and elastase levels. ETosis in semen was determined through presence of citrullinated histones, global histones, and extracellular DNA. Different ETosis phenotypes such as spread ETs, aggregated ETs, and diffuse ETs were identified by co-localisation of extruded DNA with myeloperoxidase and global histones. Anti-CD15+ and anti-CD68+ antibodies were used to identify different cell lines. RESULTS: Revealed a high number of ETs compared with the control group. The mean number of CD15+PMN and CD68+ macrophages was higher in the acute epididymitis group. ETosis increase in ejaculates correlated with clinical parameters such as enhancement of elastase concentrations and diminution of fructose in the semen. CONCLUSIONS: This work shows for the first time the presence of ETs and their components in semen from patients with acute epididymitis. The presence of infections is an important factor for induction of ETs in semen. Furthermore, the presence of ETosis in ejaculates is suggestive of developing infectious processes and might possibly have a diagnostic value.

Tumor of the epididymis: an uncommon presentation of disseminated coccidioidomycosis.

Coccidioidomycosis is an endemic disease of arid regions in the Western hemisphere. Its clinical presentation varies from asymptomatic nodules on chest x-rays to disseminated disease. We present the case of a 48-year-old man with a hard and heterogeneous tumor in the posterior aspect of the right testis. Color flow doppler testicular ultrasonography was performed and two nodular masses in the tail of the right epididymis were identified. An epididymectomy was performed and histopathological examination revealed coccidioidomycosis. After diagnosis, the patient was successfully treated with fluconazol.

S100A4 promotes the progression of lipopolysaccharide-induced acute epididymitis in mice†.

S100A4 has been suggested to be a critical regulator of tumor metastasis and is implicated in the progression of inflammation. The aim of this study is to investigate the expression and possible role of S100A4 in epididymitis. Using a mouse model of epididymitis induced by the injection of lipopolysaccharide (LPS) in the deferent duct, we found that LPS administration induced an upregulation of S100a4 transcription (P < 0.05) and a recruitment of S100A4 positive cells in the epididymal interstitium of wild type (WT) mice. Co-immunofluorescence showed that S100A4 was mainly expressed by granulocytes, CD4 lymphocytes, and macrophages. Deficiency of S100A4 reduced epididymal pathological reaction and the mRNA levels of the pro-inflammatory cytokines IL-1ß and TNF-α (P < 0.01), suggesting that S100A4 promotes the progression of epididymitis. Furthermore, S100A4 deficiency alleviated the decline of sperm motility and rectified the abnormal expression of sperm membrane protein AMAD3, which suggested that in the progression of epididymitis, S100A4 aggravates the damage to sperm vitality. In addition, both Ki-67 marked cell proliferation and transferase-mediated dUTP-biotin nick end labeling detected cell apoptosis were reduced in S100a4-/- mice compared with WT mice after LPS treatment, indicating that S100A4 promotes both cell proliferation and cell apoptosis in epididymitis. Overall, these results demonstrate that S100A4 promotes the progression of LPS-induced epididymitis and facilitates a decline in sperm vitality, and its function may be related to the process of cell proliferation and apoptosis during inflammation.

Differential tissue-specific damage caused by bacterial epididymo-orchitis in the mouse.

Ascending bacterial urinary tract infections can cause epididymo-orchitis. In the cauda epididymidis, this frequently leads to persistent tissue damage. Less coherent data is available concerning the functional consequences of epididymo-orchitis on testis and caput epididymidis. This in vivo study addresses the functional and spatial differences in responsiveness of murine epididymis and testis to infection with uropathogenic Escherichia coli (UPEC). Whole transcriptome analysis (WTA) was performed on testis, caput, corpus and cauda epididymidis of adult C57BL/6 J wildtype mice. Following UPEC-induced epididymo-orchitis in these mice, epididymal and testicular tissue damage was evaluated histologically and semi-quantitatively at 10 days and 31 days post-inoculation. Expression of inflammatory markers and candidate antimicrobial genes were analysed by RT-qPCR. WTA revealed distinct differences in gene signatures between caput and cauda epididymidis, particularly amonst immunity-related genes. Cellular and molecular signs of testicular inflammation and disruption of spermatogenesis were noticed at day 10, but recovery was observed by day 31. In contrast to the cauda, the caput epididymidis did not reveal any signs of gross morphological damage or presence of pro-inflammatory processes despite confirmed infection. In contrast to beta-defensins, known UPEC-associated antimicrobial peptides (AMP), like Lcn2, Camp and Lypd8, were inherently highly expressed or upregulated in the caput following infection, potentially allowing an early luminal protection from UPEC. At the time points investigated, the caput epididymidis was protected from any obvious infection/inflammation-derived tissue damage. Studies addressing earlier time-points will conclude whether in the caput epididymidis a pro-inflammatory response is indeed not essential for effective protection from UPEC.

An atlas overview of characteristic features of tuberculosis that may be encountered at autopsy.

Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis. Although primarily a disease of the respiratory system it may be found in any organ or tissue. Global population movements and the emergence of resistant strains are contributing to increasing numbers of cases in certain populations. Subtlety of symptoms and signs, chronicity of disease and failure to seek medical assistance may result in the diagnosis only being made at the time of autopsy. For this reason forensic pathologists need to understand the protean manifestations of the disease and the variable mechanisms by which TB may cause death. This atlas overview provides descriptions of the pathological manifestations of TB in a variety of organs with accompanying illustrations. It serves as a summary of conditions that should be checked for at autopsy in suspected or confirmed cases.

Torsion of an undescended testis - A surgical pediatric emergency.

BACKGROUND/PURPOSE: Torsion of an undescended testis is a surgical emergency whose frequency may be underestimated in the pediatric population. We describe this entity and focus on diagnostic challenges and optimal treatment of torsion of an undescended testis. METHODS: We present a two-center retrospective chart review of patients with torsion of an undescended testis treated between 2013 and 2018. Two instructive cases are used to depict characteristics of this rare entity. RESULTS: We identified 11 patients with previously diagnosed cryptorchidism undergoing surgery for torsion of an undescended testis, accounting for 9.7% (11/107) of all testicular torsions in the period. Mean age at diagnosis was 9.4 months (1-22 months). Mean duration from onset of symptoms to presentation was 19.3 h (8-48 h). At admission to hospital 10 patients presented with groin lump (10/11, 90.9%) with or without pain leading to a suspected diagnosis of inguinal testicular torsion (5/11, 45.5%), incarcerated inguinal hernia (4/11, 36.4%) and epididymitis (1/11, 9.1%). Ten patients had an ultrasound examination before surgery leading to the correct diagnosis in six patients. Ultrasound findings were misinterpreted as incarcerated inguinal hernia in three patients. In eight patients the testis had to be removed at time of surgery; one of the three salvaged testes atrophied, resulting in a salvage rate of 18%. CONCLUSION: Torsion of an inguinal testis is not as rare as it might be presumed. Presentation of these patients is often deferred owing to equivocal signs and symptoms. In addition age at presentation differs from typical testicular torsion. As this might negatively influence testicular salvage rate, we advocate for special attention to this differential diagnosis in children with groin pathologies. Even if the child is not in pain, a tender groin in boys with undescended testes must prompt a quick and thorough examination to rule out torsion of an undescended testis. Ultrasound examination is of limited value and must not delay acute surgical treatment. LEVEL OF EVIDENCE: IV.

Effect of ketotifen fumarate on experimental autoimmune orchitis and torsion of the spermatic cord.

The aim of this work was to study effects of ketotifen fumarate (KF) on prevention of tissue damage in testes of rats with experimental autoimmune orchitis (EAO) and on the contralateral testis in a model of prolonged testicular cord torsion (TCT). Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution (vehicle group). Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score. Mast cells (MC) were identified by histochemistry and quantified. In EAO model, KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group. KF also reduced the number of testicular MC compared to vehicle group. Similarly, in TCT model, multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium, seminiferous tubule atrophy, and interstitial edema. Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed. In contrast, sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features. A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals. In conclusion, we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models. The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.

Damaged male germ cells induce epididymitis in mice.

Epididymitis can be caused by infectious and noninfectious etiological factors. While microbial infections are responsible for infectious epididymitis, the etiological factors contributing to noninfectious epididymitis remain to be defined. The present study demonstrated that damaged male germ cells (DMGCs) induce epididymitis in mice. Intraperitoneal injection of the alkylating agent busulfan damaged murine male germ cells. Epididymitis was observed in mice 4 weeks after the injection of busulfan and was characterized by massive macrophage infiltration. Epididymitis was coincident with an accumulation of DMGCs in the epididymis. In contrast, busulfan injection into mice lacking male germ cells did not induce epididymitis. DMGCs induced innate immune responses in epididymal epithelial cells (EECs), thereby upregulating the pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß), as well as the chemokines such as monocyte chemotactic protein-1 (MCP-1), monocyte chemotactic protein-5 (MCP-5), and chemokine ligand-10 (CXCL10). These results suggest that male germ cell damage may induce noninfectious epididymitis through the induction of innate immune responses in EECs. These findings provide novel insights into the mechanisms underlying noninfectious epididymitis, which might aid in the diagnosis and treatment of the disease.

Melatonin protects against lipopolysaccharide-induced epididymitis in sheep epididymal epithelial cells in vitro.

Melatonin has protective effects against inflammation but its role in epididymitis is unknown. We addressed this in the present study using lipopolysaccharide (LPS)-stimulated sheep epididymal epithelial cells as an in vitro inflammation model. We found that interleukin (IL)-1ß, IL-6, tumor necrosis factor α, and cyclooxygenase (COX)-2 mRNA levels; COX-2 and Toll-like receptor (TLR)-4 protein levels; and nuclear factor (NF)-κB p65 phosphorylation were increased by LPS treatment. These effects were reversed in a dose-dependent manner by melatonin (10-11-10-7 M). Quantitative reverse transcription PCR and immunofluorescence analyses showed that the melatonin receptors MT1 and MT2 were expressed in sheep epididymal epithelial cells. The inhibitory effect of melatonin on inflammation was abrogated by the MT1 and MT2 receptor antagonist luzindole and the MT2 ligand 4-phenyl-2-propanamide tetraldehyde. Thus, melatonin exerted anti-inflammatory effect in epididymal epithelial cells by inhibiting TLR4/NF-κB signaling, suggesting its potential as an effective drug for the treatment of epididymitis in sheep.

Activins, follistatin and immunoregulation in the epididymis.

BACKGROUND: The interface between the epididymis and the immune system is implicated in many male reproductive pathologies. The resident immune cell populations and immune-environment within the epididymis are significantly different from the testis, which is an immune-privileged site. Moreover, the immune cell subsets and immunological responses between different regions of the epididymis vary considerably. The cauda epididymis is more susceptible to autoimmune responses than the caput in rodent models of active immunization or suppressed immune tolerance, and in men with congenital or physical damage to the reproductive tract. Activins are members of the transforming growth factor-ß family of cytokines that are crucial for testis and epididymal development; however, they also have complex immunoregulatory properties and may play an essential role in the regulation of immunity in the reproductive tract. MATERIALS AND METHODS: Our recent research and relevant publications by other researchers identified following a PubMed search are reviewed. RESULTS: The caput epididymis displays elevated endogenous expression of activins A and B and the immunoregulatory gene, indoleamine-2,3-dioxygenase, co-existing with an extensive population of intra-epithelial and interstitial macrophages and dendritic cells, which appear to be involved in regulating tolerance against sperm antigens. The caput is also relatively resistant to inflammatory damage caused by autoimmunity or bacterial infection, but the cauda, which exhibits low activin expression and high levels of the activin-binding protein, follistatin, is highly susceptible to inflammatory damage. Paradoxically, inflammation in the cauda induces increased activin production, and inhibition of activin activity reduces inflammatory responses. Studies using mouse models with altered levels of activins and follistatin indicate a relationship between the activins and genes involved in inflammation and immunoregulation. CONCLUSION: The existing data indicate that activins play a complex role in controlling inflammation and immunity in the epididymis and vas deferens.

Dexamethasone improves therapeutic outcomes in a preclinical bacterial epididymitis mouse model.

STUDY QUESTION: Can dexamethasone improve infertility-related cauda epididymidal tissue damage caused by bacterial epididymitis? SUMMARY ANSWER: Dexamethasone in addition to anti-microbial treatment effectively reduces long-term deleterious epididymal tissue damage by dampening the host's adaptive immune response. WHAT IS KNOWN ALREADY: Despite effective anti-microbial treatment, ~40% of patients with epididymitis experience subsequent sub- or infertility. An epididymitis mouse model has shown that the host immune response is mainly responsible for the magnitude of epididymal tissue damage that is fundamentally causative of the subsequent fertility issues. STUDY DESIGN, SIZE, DURATION: Bacterial epididymitis was induced in male mice by using uropathogenic Escherichia coli (UPEC). From Day 3 after infection onwards, mice were treated with daily doses of levofloxacin (20 mg/kg, total n = 12 mice), dexamethasone (0.5 mg/kg, total n = 9) or both in combination (total n = 11) for seven consecutive days. Control animals were left untreated, i.e. given no interventional treatment following UPEC infection (total n = 11). Half of the animals from each group were killed either at 10 or 31 days post-infection. PARTICIPANTS/MATERIALS, SETTING, METHODS: A mouse model of induced bacterial epididymitis was applied to adult male C57BL/6J mice. At the respective endpoints (10 or 31 days post-infection), epididymides were collected. Effectiveness of antibiotic treatment was assessed by plating of epididymal homogenates onto lysogeny broth agar plates. Overall tissue morphology and the degree and nature of tissue damage were assessed histologically. Quantitative RT-PCR was used to assess local cytokine transcript levels. Blood was drawn and serum analysed for systemic IgG and IgM levels by ELISA. In addition, correlation analyses of clinical data and serum-analyses of IgG and IgM levels in patients with epididymitis were performed. MAIN RESULTS AND THE ROLE OF CHANCE: The addition of dexamethasone to the standard anti-microbial treatment did not further worsen epididymal tissue integrity. In fact, an obviously dampened immune response and reduced tissue reaction/damage was observed at both 10 and 31 days post-infection following combined treatment. More specifically, epididymal duct continuity was preserved, enabling sperm transit. In contrast, in untreated or antibiotic-treated animals, damage of the epididymal duct and duct constrictions were observed, associated with a lack of cauda spermatozoa. In line with the bacteriostatic/bactericidal effect of levofloxacin (alone as well as in combination), local cytokine transcript levels were significantly and similarly reduced in animals treated with levofloxacin alone (P < 0.01) or in combination with dexamethasone (P < 0.05) compared to UPEC-infected untreated animals. Interestingly, the addition of dexamethasone to the anti-microbial treatment induced a unique dampening effect on adaptive immunity, since systemic IgG and IgM levels as well as the pan-T cell marker CD3 were reduced at both 10 and 31 days post-infection. LIMITATIONS, REASONS FOR CAUTION: Breeding studies to address the fertility-protecting effect of the combined treatment were not possible in the experimental animals because the vas deferens was ligated (model specific). WIDER IMPLICATIONS OF THE FINDINGS: Whereas innate immunity is necessary and involved in acute bacterial clearance, adaptive immunity seems to be responsible for long-term, subclinical immunological activities that may negatively affect the pathogenesis of bacterial epididymitis even after effective bacterial eradication. These effects can be reduced in mice by the additional treatment with dexamethasone. This immunological characteristic of bacterial epididymitis shows similarities to the Jarisch-Herxheimer reaction known from other types of bacterial infection. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by grants from the Deutsche Forschungsgemeinschaft, Monash University and the Medical Faculty of Justus-Liebig University to the International Research Training Group on 'Molecular pathogenesis of male reproductive disorders' (GRK 1871). R.W., K.L.L. and M.P.H. were supported by grants from the National Health and Medical Research Council of Australia (ID1079646, ID1081987, ID1020269 and ID1063843) and by the Victorian Government's Operational Infrastructure Support Program. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: No clinical trial involved.

In search of new paradigms for epididymal health and disease: innate immunity, inflammatory mediators, and steroid hormones.

The primary job of the epididymis is to mature and protect the luminally transiting spermatozoa. Mounting evidence is showing that innate immune components [including Toll-like receptors (TLRs) and antimicrobial proteins, among which are ß-defensins] and inflammatory mediators, under the primary influence of androgens, participate in the cellular and molecular processes that define this tissue. Here, we present an overview of the contributions of these signaling pathway components during epididymal homeostasis and discuss the hypotheses as to their involvement in epididymitis, the most common urological inflammatory condition in men, frequently impairing their fertility. Drawing primarily from rodent models, we also focus on how the distribution and functional expression of innate immune components are differentially regulated in the prenatal developing epididymis, providing new insights into the disruption of these signaling pathways throughout the lifespan. Male infertility is caused by a variety of conditions, such as congenital malformations, genetic and endocrine disorders, exposure to environmental toxicants, and inflammatory/infectious conditions. More than one-third of infertile men with an idiopathic condition cannot currently be adequately diagnosed. Thinking about the innate immunity and inflammation context of the epididymis may provide new insights and directions as to how these systems contribute to male fertility, as well as also uncover urological and andrological outcomes that may aid clinicians in diagnosing and preventing epididymal pathologies.

[Orchitis]. / Hodenentzündung.

Orchitis can be acutely symptomatic or chronically asymptomatic. Among the acute forms is the rarer isolated orchitis, which is of viral origin in most cases as well as the more frequent secondary orchitis, which is usually the result of an ascending bacterial epididymitis. In addition, sterile forms of orchitis are also seen in patients with systemic autoimmune comorbidities. Chronic asymptomatic orchitis is the term used to describe cellular immune infiltrates in the testes, which are observed in approximately 25% of cases of azoospermia during testicular biopsy. The etiopathogenesis of these infiltrates is largely unknown with postinfection and primary pathogen-independent autoimmune reactions being discussed. Animal experimental models of orchitis may be helpful to investigate the immunological mechanisms involved as well as the therapeutic possibilities.