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Urology Case Reports Sep 2019Intravesical immunotherapy with Bacillus Calmette-Guerin has been shown to decrease tumor recurrence and progression in urothelial carcinoma of the bladder. Its...
Intravesical immunotherapy with Bacillus Calmette-Guerin has been shown to decrease tumor recurrence and progression in urothelial carcinoma of the bladder. Its ubiquitous use is further substantiated by its low rates of complications. Our patient is a 63 year old male with a circuitous medical course who presents with epididymoorchitis and scrotal abscess after his second three week cycle of maintenance BCG prompting scrotal exploration which revealed a non-viable testicle and large scrotal induration with abscess. Pathological analysis and initial cultures were negative for mycobacterium but acid-fast cultures eventually demonstrated mycobacterium three months later.
PubMed: 31198685
DOI: 10.1016/j.eucr.2019.100925 -
Journal of Biomedical Science Feb 2023Zika virus (ZIKV) infection is clinically known to induce testicular swelling, termed orchitis, and potentially impact male sterility, but the underlying mechanisms...
BACKGROUND
Zika virus (ZIKV) infection is clinically known to induce testicular swelling, termed orchitis, and potentially impact male sterility, but the underlying mechanisms remain unclear. Previous reports suggested that C-type lectins play important roles in mediating virus-induced inflammatory reactions and pathogenesis. We thus investigated whether C-type lectins modulate ZIKV-induced testicular damage.
METHODS
C-type lectin domain family 5 member A (CLEC5A) knockout mice were generated in a STAT1-deficient immunocompromised background (denoted clec5astat1) to enable testing of the role played by CLEC5A after ZIKV infection in a mosquito-to-mouse disease model. Following ZIKV infection, mice were subjected to an array of analyses to evaluate testicular damage, including ZIKV infectivity and neutrophil infiltration estimation via quantitative RT-PCR or histology and immunohistochemistry, inflammatory cytokine and testosterone detection, and spermatozoon counting. Furthermore, DNAX-activating proteins for 12 kDa (DAP12) knockout mice (dap12stat1) were generated and used to evaluate ZIKV infectivity, inflammation, and spermatozoa function in order to investigate the potential mechanisms engaged by CLEC5A.
RESULTS
Compared to experiments conducted in ZIKV-infected stat1 mice, infected clec5astat1 mice showed reductions in testicular ZIKV titer, local inflammation and apoptosis in testis and epididymis, neutrophil invasion, and sperm count and motility. CLEC5A, a myeloid pattern recognition receptor, therefore appears involved in the pathogenesis of ZIKV-induced orchitis and oligospermia. Furthermore, DAP12 expression was found to be decreased in the testis and epididymis tissues of clec5astat1 mice. As for CLEC5A deficient mice, ZIKV-infected DAP12-deficient mice also showed reductions in testicular ZIKV titer and local inflammation, as well as improved spermatozoa function, as compared to controls. CLEC5A-associated DAP12 signaling appears to in part regulate ZIKV-induced testicular damage.
CONCLUSIONS
Our analyses reveal a critical role for CLEC5A in ZIKV-induced proinflammatory responses, as CLEC5A enables leukocytes to infiltrate past the blood-testis barrier and induce testicular and epididymal tissue damage. CLEC5A is thus a potential therapeutic target for the prevention of injuries to male reproductive organs in ZIKV patients.
Topics: Humans; Male; Mice; Animals; Zika Virus; Zika Virus Infection; Orchitis; Semen; Mice, Knockout; Inflammation; Lectins, C-Type; Receptors, Cell Surface
PubMed: 36803804
DOI: 10.1186/s12929-023-00906-6 -
Urology Annals 2023Epididymo-orchitis (EO) is a common urological condition. In endemic areas, EO may be the presenting picture of brucellosis. Early suspicion and proper diagnosis is...
INTRODUCTION
Epididymo-orchitis (EO) is a common urological condition. In endemic areas, EO may be the presenting picture of brucellosis. Early suspicion and proper diagnosis is necessary for patient recovery.
OBJECTIVE
The aim of our study is to identify early predictors of EO.
PATIENTS AND METHODS
We retrospectively collected the data of all patients who were treated at the Urology Unit, Farwaniya Hospital, with acute EO above the age of 12 years between April 2017 and February 2019. Data from electronic and hardcopy files were gathered and analyzed. The diagnosis of acute EO was based on clinical, laboratory, and radiological findings. A total of 120 patients under the diagnosis of EO, epididymitis, and orchitis were reviewed. Thirty-one patients were tested for based on the history of animal contact, ingestion of unpasteurized dairy products, or persistent fever for more than 48 h. of those patients, 11 tested positive for orchitis.
RESULTS
A comparison between -positive and -negative patients regarding age, presence of fever, complete blood count (CBC) parameters, pyuria, and abscess formation was made. In the group, 72% of the patients had a history of animal contact compared to 33% in non- group ( = 0.006). When comparing CBC parameters in the two groups, group had statistically significant lower total leukocytic count and neutrophil count (mean ± standard deviation [SD]) 13.07 ± 4.22, 6.4 ± 9.98 versus negative group 17.35 ± 5.28, 7.8 ± 10.53, and values were 0.037 and 0.004, respectively. group showed lymphocytosis (mean ± SD) 25.95 ± 9.78 versus non- group 13.22 ± 8.05 and < 0.01.
CONCLUSION
orchitis constituted 9% of the orchitis patients treated in our hospital. Patients with a history of animal contact, EO with lymphocytosis, and relative neutropenia should raise the suspicion for orchitis in endemic areas.
PubMed: 37304522
DOI: 10.4103/ua.ua_178_21 -
Proceedings of the National Academy of... Sep 2023Regulatory T cells (Tregs) modulate tissue homeostatic processes and immune responses. Understanding tissue-Treg biology will contribute to developing...
Regulatory T cells (Tregs) modulate tissue homeostatic processes and immune responses. Understanding tissue-Treg biology will contribute to developing precision-targeting treatment strategies. Here, we show that Tregs maintain the tolerogenic state of the testis and epididymis, where sperm are produced and mature. We found that Treg depletion induces severe autoimmune orchitis and epididymitis, manifested by an exacerbated immune cell infiltration [CD4 T cells, monocytes, and mononuclear phagocytes (MPs)] and the development of antisperm antibodies (ASA). In Treg-depleted mice, MPs increased projections toward the epididymal lumen as well as invading the lumen. ASA-bound sperm enhance sperm agglutination and might facilitate sperm phagocytosis. Tolerance breakdown impaired epididymal epithelial function and altered extracellular vesicle cargo, both of which play crucial roles in the acquisition of sperm fertilizing ability and subsequent embryo development. The affected mice had reduced sperm number and motility and severe fertility defects. Deciphering these immunoregulatory mechanisms may help to design new strategies to treat male infertility, as well as to identify potential targets for immunocontraception.
Topics: Male; Animals; Mice; Humans; T-Lymphocytes, Regulatory; Semen; Spermatozoa; Immune Tolerance; Antibodies; Fertility
PubMed: 37676910
DOI: 10.1073/pnas.2306797120 -
Frontiers in Immunology 2020Infection and inflammation of the male reproductive tract are relevant causes of infertility. Inflammatory damage occurs in the special immunosuppressive... (Review)
Review
Infection and inflammation of the male reproductive tract are relevant causes of infertility. Inflammatory damage occurs in the special immunosuppressive microenvironment of the testis, a hallmark termed testicular immune privilege, which allows tolerance to neo-antigens from developing germ cells appearing at puberty, long after the establishment of systemic immune tolerance. Experimental autoimmune orchitis (EAO) is a well-established rodent model of chronic testicular inflammation and organ specific autoimmunity that offers a valuable tool to investigate the pathological and molecular mechanisms leading to the breakdown of the testicular immune privilege. The disease is characterized by the infiltration of the interstitium by immune cells (mainly macrophages, dendritic cells, and T cells), formation of autoantibodies against testicular antigens, production of pro-inflammatory mediators such as NO, MCP1, TNFα, IL6, or activins and dysregulation of steroidogenesis with reduced levels of serum testosterone. EAO leads to sloughing of germ cells, atrophic seminiferous tubules and fibrotic remodeling, parameters all found similarly to changes in human biopsies from infertile patients with inflammatory infiltrates. Interestingly, testosterone supplementation during the course of EAO leads to expansion of the regulatory T cell population and inhibition of disease development. Knowledge of EAO pathogenesis aims to contribute to a better understanding of human testicular autoimmune disease as an essential prerequisite for improved diagnosis and treatment.
Topics: Animals; Autoimmune Diseases; Humans; Male; Orchitis
PubMed: 33101310
DOI: 10.3389/fimmu.2020.583135 -
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 -
European Review For Medical and... Jan 2021The objective of this review is to provide currently available information on the potential effects of coronavirus disease 2019 (COVID-19) on male fertility. (Review)
Review
OBJECTIVE
The objective of this review is to provide currently available information on the potential effects of coronavirus disease 2019 (COVID-19) on male fertility.
MATERIALS AND METHODS
This is a mini-review. Due to the similarity between the COVID-19 and severe acute respiratory syndrome (SARS) virus, we searched for the following keywords: "SARS-CoV, male reproductive system, infertility, COVID-19, SARS-CoV-2, and orchitis". By reviewing and analyzing the literature, we analyzed the influence of temperature on sperm, the expression of angiotensin-converting enzyme 2 (ACE2) in the testes, and the impact of SARS-CoV-2 on the male reproductive system.
RESULTS
SARS-CoV-2 enters the body through the ACE2 receptor. The high expression of ACE2 on the surface of spermatogonia and supporting cells in the testes, as well as the immune response caused by COVID-19, can lead to testicular spermatogenesis dysfunction and reduced sperm count.
CONCLUSIONS
COVID-19 infection can affect male reproductive function, and standard treatment strategies should be established in time to help male patients infected with COVID-19.
Topics: Angiotensin-Converting Enzyme 2; COVID-19; Genitalia, Male; Humans; Male; Orchitis; Spermatozoa
PubMed: 33577068
DOI: 10.26355/eurrev_202101_24682 -
Andrologia Feb 2021COVID-19 pandemic leads to health challenges globally, and its diverse aspects need to be uncovered. Multi-organ injuries have been reported by describing potential... (Review)
Review
COVID-19 pandemic leads to health challenges globally, and its diverse aspects need to be uncovered. Multi-organ injuries have been reported by describing potential SARS-CoV-2 entrance routes: ACE2 and TMPRSS2. Since these cell surface receptors' expression has been disclosed within the male reproductive system, its susceptibility to being infected by SARS-CoV-2 has been summarised through this literature review. Expression of ACE2 and TMPRSS2 at RNA or protein level has been reported across various investigations indicates that the male genitalia potentially is vulnerable to SARS-CoV-2 infection. Presence of SARS-CoV-2 within semen samples and following direct viral damage, secondary inflammatory response causing orchitis or testicular discomfort and finally the amount of viral load leading testicular damage and immune response activation are among probable underlying mechanisms. Therefore, genital examination and laboratory tests should be considered to address the male reproductive tract complications and fertility issues.
Topics: Angiotensin-Converting Enzyme 2; COVID-19; Genitalia, Male; Humans; Infertility, Male; Male; Orchitis; RNA, Messenger; SARS-CoV-2; Semen; Serine Endopeptidases; Spike Glycoprotein, Coronavirus; Testis
PubMed: 33236375
DOI: 10.1111/and.13914