-
EMBO Molecular Medicine Feb 2024Inflammation in the testes induced by infection and autoimmunity contributes significantly to male infertility, a public health issue. Current therapies using...
Inflammation in the testes induced by infection and autoimmunity contributes significantly to male infertility, a public health issue. Current therapies using antibiotics and broad-spectrum anti-inflammatory drugs are ineffective against non-bacterial orchitis and induce side effects. This highlights the need to explore the pathogenesis of orchitis and develop alternative therapeutic strategies. In this study, we demonstrated that Gasdermin D (GSDMD) was activated in the testes during uropathogenic Escherichia coli (UPEC)-induced acute orchitis, and that GSDMD in macrophages induced inflammation and affected spermatogenesis during acute and chronic orchitis. In testicular macrophages, GSDMD promoted inflammation and antigen presentation, thereby enhancing the T-cell response after orchitis. Furthermore, the pharmacological inhibition of GSDMD alleviated the symptoms of UPEC-induced acute orchitis. Collectively, these findings provide the first demonstration of GSDMD's role in driving orchitis and suggest that GSDMD may be a potential therapeutic target for treating orchitis.
Topics: Male; Humans; Orchitis; Gasdermins; Antigen Presentation; Inflammation; Macrophages; Pyroptosis
PubMed: 38177538
DOI: 10.1038/s44321-023-00016-8 -
British Medical Journal (Clinical... Oct 1981
Topics: Adult; Epididymitis; Humans; Male; Orchitis
PubMed: 6794787
DOI: No ID Found -
Medical Ultrasonography Aug 2019In brucellosis the male genitourinary system can be affected in a small number of patients. In this study we aimed to identify, discuss and compare the radiologic... (Comparative Study)
Comparative Study
AIM
In brucellosis the male genitourinary system can be affected in a small number of patients. In this study we aimed to identify, discuss and compare the radiologic findings of 24 cases with Brucella epididymo-orchitis (BEO) and 285 cases with non-Brucella epididymis orchitis (NBEO).
MATERIAL AND METHODS
The study had a retrospective design. The area of involvement, side of involvement (left, right or bilateral), presence of abscess, hydrocele and testicular involvement pattern were analyzed and compared between the BEO and NBEO cases.
RESULTS
The median age of the included cases was 33 years, with a minimum of 0 and maximum of 89. Epididymo-orchitis and isolated orchitis were more frequent in BEO cases while isolated epididymis involvement was more common in patients with non-BEO (p=0.0117). Bilateral involvement was present in 20.8% and 4.6% cases in the BEO and non-BEO groups, respectively (p=0.008). The frequency of abscess was significantly higher in BEO cases (p=0.003).
CONCLUSION
Although the radiological indications of BEO are similar to those of other types of epididymo-orchitis, abscess formation, bilateral involvement and testicular involvement contribute significantly to diagnosis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brucella; Brucellosis; Child; Child, Preschool; Epididymis; Epididymitis; Humans; Infant; Male; Middle Aged; Orchitis; Retrospective Studies; Testis; Ultrasonography; Young Adult
PubMed: 31476203
DOI: 10.11152/mu-1871 -
The Journal of International Medical... May 2021We report the disease characteristics, diagnosis, and treatment of granulomatous orchitis. A 38-year-old man presented with a history of intermittent swelling, pain, and... (Review)
Review
We report the disease characteristics, diagnosis, and treatment of granulomatous orchitis. A 38-year-old man presented with a history of intermittent swelling, pain, and discomfort in the right testicle of 3 days' duration. Unenhanced magnetic resonance imaging (MRI) of the testis and scrotum revealed an oval mass in the right testis measuring approximately 17 mm in diameter, with clear borders and a target ring-like appearance from periphery to center. T1-weighted imaging (T1WI) showed uniform low-intensity signals, and T2WI showed mixed high- and low-intensity signals. Diffusion-weighted imaging (DWI) signals were iso-intense, and the outer ring on enhanced scans showed progressive enhancement. We performed radical resection of the right testis under combined spinal-epidural anesthesia. The pathological diagnosis was granulomatous right orchitis. Two months postoperatively, ultrasonography showed no testis and epididymal echo signals in the right scrotum, and no obvious abnormalities; color Doppler blood flow imaging (CDFI) findings were normal. Granulomatous orchitis is rare in clinical practice, and the cause is unknown. The disease involves non-specific inflammation; however, it is currently believed that antibiotics and steroids are ineffective for conservative treatment, and orchiectomy should be actively performed.
Topics: Adult; Diagnosis, Differential; Humans; Male; Orchiectomy; Orchitis; Scrotum; Testis
PubMed: 34041951
DOI: 10.1177/03000605211003773 -
Frontiers in Immunology 2022Continuous exposure of tissue antigen (Ag) to the autoantigen-specific regulatory T cells (Treg) is required to maintain Treg-dependent systemic tolerance. Thus, testis... (Review)
Review
Continuous exposure of tissue antigen (Ag) to the autoantigen-specific regulatory T cells (Treg) is required to maintain Treg-dependent systemic tolerance. Thus, testis autoantigens, previously considered as sequestered, may not be protected by systemic tolerance. We now document that the complete testis antigen sequestration is not valid. The haploid sperm Ag lactate dehydrogenase 3 (LDH3) is continuously exposed and not sequestered. It enters the residual body (RB) to egress from the seminiferous tubules and interact with circulating antibody (Ab). Some LDH3 also remains inside the sperm cytoplasmic droplets (CD). Treg-depletion in the DEREG mice that express diphtheria toxin receptor on the Foxp3 promoter results in spontaneous experimental autoimmune orchitis (EAO) and Ab to LDH3. Unlike the wild-type male mice, mice deficient in LDH3 (wild-type female or LDH3 males) respond vigorously to LDH3 immunization. However, partial Treg depletion elevated the wild-type male LDH3 responses to the level of normal females. In contrast to LDH3, zonadhesin (ZAN) in the sperm acrosome displays properties of a sequestered Ag. However, when ZAN and other sperm Ag are exposed by vasectomy, they rapidly induce testis Ag-specific tolerance, which is terminated by partial Treg-depletion, leading to bilateral EAO and ZAN Ab response. We conclude that some testis/sperm Ag are normally exposed because of the unique testicular anatomy and physiology. The exposed Ag: 1) maintain normal Treg-dependent systemic tolerance, and 2) are pathogenic and serve as target Ag to initiate EAO. Unexpectedly, the sequestered Ags, normally non-tolerogenic, can orchestrate Treg-dependent, systemic tolerance when exposed in vasectomy.
Topics: Animals; Autoantigens; Female; Humans; Immune Tolerance; Male; Mice; Orchitis; T-Lymphocytes, Regulatory; Vasectomy
PubMed: 35693780
DOI: 10.3389/fimmu.2022.809247 -
Cellular and Molecular Life Sciences :... Nov 2022Experimental autoimmune-orchitis (EAO), a rodent model of chronic testicular inflammation and fibrosis, replicates pathogenic changes seen in some cases of human...
Experimental autoimmune-orchitis (EAO), a rodent model of chronic testicular inflammation and fibrosis, replicates pathogenic changes seen in some cases of human spermatogenic disturbances. During EAO, increased levels of pro-inflammatory and pro-fibrotic mediators such as TNF, CCL2, and activin A are accompanied by infiltration of leukocytes into the testicular parenchyma. Activin A levels correlate with EAO severity, while elevated CCL2 acting through its receptor CCR2 mediates leukocyte trafficking and recruits macrophages. CCR2 + CXCR4 + macrophages producing extracellular matrix proteins contribute widely to fibrogenesis. Furthermore, testicular macrophages (TMs) play a critical role in organ homeostasis. Therefore, we aimed to investigate the role of the activin A/CCL2-CCR2/macrophage axis in the development of testicular fibrosis. Following EAO induction, we observed lower levels of organ damage, collagen deposition, and leukocyte infiltration (including fibronectin, collagen I and CXCR4 TMs) in Ccr2 mice than in WT mice. Furthermore, levels of Il-10, Ccl2, and the activin A subunit Inhba mRNAs were lower in Ccr2 EAO testes. Notably, fibronectin TMs were also present in biopsies from patients with impaired spermatogenesis and fibrotic alterations. Overexpression of the activin A antagonist follistatin reduced tissue damage and collagen I TM accumulation in WT EAO testes, while treating macrophages with activin A in vitro increased the expression of Ccr2, Fn1, Cxcr4, and Mmp2 and enhanced migration along a CCL2 gradient; these effects were abolished by follistatin. Taken together, our data indicate that CCR2 and activin A promote fibrosis during testicular inflammation by regulating macrophage function. Inhibition of CCR2 or activin A protects against damage progression, offering a promising avenue for therapeutic intervention.
Topics: Male; Humans; Mice; Animals; Orchitis; Follistatin; Fibronectins; Macrophages; Fibrosis; Inflammation; Receptors, CCR2
PubMed: 36434305
DOI: 10.1007/s00018-022-04632-4 -
International Journal of Clinical... Mar 2021This study aims to analyse the novel Coronavirus disease- (COVID-19) related testicular pain in hospitalised patients because of COVID-19 and to review as an...
AIMS
This study aims to analyse the novel Coronavirus disease- (COVID-19) related testicular pain in hospitalised patients because of COVID-19 and to review as an aetiological factor for epididymitis, orchitis or both.
METHODS
A total of 91 patients were included in the study. A questionnaire was formed for the questioning of testicular pain or epididymo-orchitis in patients with COVID-19. Demographics and past medical history was also recorded. Patients' neutrophil and lymphocyte counts, neutrophil-lymphocyte ratios (NLR), C-reactive protein (CRP) levels and D-dimer values were recorded. Patients with COVID-19 were divided into two groups according to absence or presence of testicular pain or epididymo-orchitis as group 1 and group 2. All results were compared for both groups.
RESULTS
The median age of patients was similar in both groups. Testicular pain was occurred in 10.98% of the patients. Clinical presentation of epididymo-orchitis was diagnosed in only one patient. No statistically significant difference was reported in terms of patients' age, levels of CRP and D-Dimer or NLR and results of questionnaire form queries between the two groups (P > .05).
CONCLUSION
Testicular pain was observed more frequently in hospitalised COVID-19 cases. While no inflammation marker which is related to predict of testicular pain or epididymo-orchitis was found in patients with COVID-19.
Topics: COVID-19; Epididymitis; Humans; Male; Orchitis; Pain; SARS-CoV-2
PubMed: 33063899
DOI: 10.1111/ijcp.13753 -
Case Reports in Urology 2022Epididymo-orchitis is an infection of the epididymis and testis, one of the most common urogenital infections. It can be seen at any age. It is caused by sexually...
Epididymo-orchitis is an infection of the epididymis and testis, one of the most common urogenital infections. It can be seen at any age. It is caused by sexually transmitted microorganisms and nonsexual transmitted pathogens. Viruses such as mumps and cytomegalovirus can also cause epididymo-orchitis. During the COVID-19 pandemic, in case of abnormal clinical manifestations of COVID infection and inadequate therapeutic response to the routine therapies, this disease with unusual manifestations should be considered. The case introduced in this paper is a 55-year-old man referred to a urology clinic with typical clinical presentations of epididymo-orchitis. Diagnosis by color Doppler examination and ultrasound also confirmed epididymo-orchitis. The patient underwent appropriate and routine treatment for epididymo-orchitis. Because of the lack of adequate clinical response and the continuation of fever and the development of scrotal lesions and the results of the control ultrasound, which suggested rupture of the tunica albuginea capsule, he underwent surgical exploration and subsequent orchiectomy. Due to the unconventional conditions and the usual culture and pathology, COVID-19 PCR was also performed on the tissues. The PCR showed tissue infection with COVID-19. The patient's clinical condition improved with an orchiectomy, the fever stopped, and he was discharged in a good general condition. It should be noted that before referral to the urology clinic and during hospitalization, evaluation, and treatment, the patient had no evidence in favor of respiratory tract infection with the coronavirus.
PubMed: 35795005
DOI: 10.1155/2022/1891429 -
Frontiers in Immunology 2022
Topics: Male; Humans; Orchitis; Epididymitis; Genitalia, Male
PubMed: 36325325
DOI: 10.3389/fimmu.2022.1042468 -
Ultrasonography (Seoul, Korea) Jul 2020The purpose of this study was to describe the ultrasonographic findings of testicular atrophy after mumps orchitis.
PURPOSE
The purpose of this study was to describe the ultrasonographic findings of testicular atrophy after mumps orchitis.
METHODS
We retrospectively reviewed the case files of eight patients (14 to 24 years old; mean, 17 years) with mumps orchitis and testicular atrophy who were treated between January 2011 and September 2017. On gray-scale and color Doppler, the ultrasonographic features of volume, shape, echogenicity, and degree of blood flow in the testes were analyzed as part of both initial and follow-up ultrasonography. The duration between the initial diagnosis of mumps orchitis and the ultrasonographic diagnosis of testicular atrophy after mumps orchitis ranged from 25 to 230 days (mean, 95.9 days).
RESULTS
Of the eight patients with testicular atrophy after mumps orchitis, the testes were affected unilaterally in seven patients (6 right-sided and 1 left-sided) and bilaterally in one patient. The affected testes (n=9) were 23%-55% (mean, 44.7%) smaller in volume (mean, 6.3±2.0 mL) than the contralateral normal testes (n=7) (mean, 10.8±2.3 mL) on follow-up ultrasonography (P=0.001). The shape of the atrophic testes was oblong in seven cases and elliptical in two cases. The atrophic testes were either heterogeneously hypoechoic with multiple hyperechoic islands (n=7) or heterogeneously hyperechoic (n=2). On follow-up color Doppler ultrasonography, the degree of vascularity of the atrophic testis was either similar to (n=3) or lower than (n=6) that of the contralateral testis.
CONCLUSION
On ultrasonography, atrophic testes after mumps orchitis tended to exhibit an oblong shape, heterogeneous low echogenicity with multiple hyperechoic islands, and decreased vascularity.
PubMed: 32299198
DOI: 10.14366/usg.19097