RESUMO
Experimental autoimmune orchitis (EAO) is a well-established rodent model of organ-specific autoimmunity associated with infertility in which the testis immunohistopathology has been extensively studied. In contrast, analysis of testis biopsies from infertile patients associated with inflammation has been more limited. In this work, testicular biopsies from patients with idiopathic non-obstructive azoospermia diagnosed with hypospermatogenesis (HypoSp) [mild: n = 9, and severe: n = 11], with obstructive azoospermia and complete Sp (spermatogenesis) (control group, C, n = 9), and from Sertoli cell-only syndrome (SCOS, n = 9) were analyzed for the presence of immune cells, spermatogonia and Sertoli cell (SCs) alterations, and reproductive hormones levels. These parameters were compared with those obtained in rats with EAO. The presence of increased CD45+ cells in the seminiferous tubules (STs) wall and lumen in severe HypoSp is associated with increased numbers of apoptotic meiotic germ cells and decreased populations of undifferentiated and differentiated spermatogonia. The SCs showed an immature profile with the highest expression of AMH in patients with SCOS and severe HypoSp. In SCOS patients, the amount of SCs/ST and Ki67+ SCs/ST increased and correlated with high serum FSH levels and CD45+ cells. In the severe phase of EAO, immune cell infiltration and apoptosis of meiotic germ cells increased and the number of undifferentiated and differentiated spermatogonia was lowest, as previously reported. Here, we found that orchitis leads to reduced sperm number, viability, and motility. SCs were mature (AMH-) but increased in number, with Ki67+ observed in severely damaged STs and associated with the highest levels of FSH and inflammatory cells. Our findings demonstrate that in a scenario where a chronic inflammatory process is underway, FSH levels, immune cell infiltration, and immature phenotypes of SCs are associated with severe changes in spermatogenesis, leading to azoospermia. Furthermore, AMH and Ki67 expression in SCs is a distinctive marker of severe alterations of STs in human orchitis.
RESUMO
Although several testicular alterations promoted by coronavirus infection have been demonstrated, the extent, causes, and players of testicular pathogenesis are not totally understood. The present study aimed to investigate the short-term effects on male fertility of intranasally administered murine hepatitis virus strain 3 (MHV-3), a member of the genus Betacoronavirus, which causes a severe systemic acute infection. This mouse model might be used as a in vivo prototype for investigating the impact of betacoronavirus on the endocrine and exocrine testicular functions with the advantage to be performed in a biosafety level 2 condition. Herein, we performed virological, histopathological, and molecular studies regarding the testicular spermatogenesis and the spermatic quality analyses in an MHV-3-infected C57BL/6 mice. The main outcomes showed that MHV-3 infects mouse testis and induces a testicular inflammatory state, impairing the steroidogenic pathway. The infection led to several alterations in the testicular parenchyma, such as: seminiferous epithelium sloughing, retention of residual bodies, germ cell apoptosis, alterations in intercellular junction proteins, and worse spermatogenic parameters. Moreover, the levels of plasmatic testosterone as well as the quality of sperm production reduced. Therefore, the present data suggest that the viral/inflammatory impairment of the steroidogenic pathway and the consequent imbalance of androgen levels is critical in testicular pathology, disturbing the SC barrier function and the germ cell differentiation. Our study is important for comprehending the effects of beta coronavirus infections on testis function in order to develop treatments that could prevent virus-mediated male infertility.
Assuntos
Camundongos Endogâmicos C57BL , Vírus da Hepatite Murina , Espermatogênese , Espermatozoides , Testículo , Animais , Masculino , Camundongos , Testículo/virologia , Testículo/patologia , Testículo/imunologia , Espermatozoides/virologia , Espermatozoides/imunologia , Espermatozoides/patologia , Modelos Animais de Doenças , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Infecções por Coronavirus/imunologia , Infertilidade Masculina/virologia , Infertilidade Masculina/imunologia , Infertilidade Masculina/patologia , Infertilidade Masculina/etiologia , Testosterona/sangue , HumanosRESUMO
This study included 47 free-ranging bats from the State of Minas Gerais, Brazil. Six bats (12.8%) had genital inflammatory lesions, and two of them (one Artibeus lituratus and one Glossophaga soricina, a frugivorous and a nectarivorous, respectively) were diagnosed with Brucella sp. infection through PCR, and antigens in intralesional macrophages were detected using immunohistochemistry.
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El compromiso genitourinario en una infección causada por Salmonella spp es poco frecuente, especialmente en niños. Se presenta un paciente de 40 días de vida que presentó una orquiepididimitis por Salmonella entérica serotipo Newport, con documentación microbiológica en hemocultivos, cultivo de secreción escrotal y coprocultivo. No presentó compromiso del sistema nervioso central. Un tratamiento médico y quirúrgico tempranos permitieron la evolución favorable del paciente.
Genitourinary involvement in a Salmonella spp infection is rare, especially in pediatric patients. A 40-day-old patient who presented an orchiepididymitis due to Salmonella enterica Serotype Newport is reported, with microbiological documentation in blood cultures, culture of scrotal purulent material and stool culture. There was no involvement of the central nervous system. Early medical and surgical treatment allowed the favorable evolution of the patient.
Assuntos
Humanos , Masculino , Lactente , Orquite/microbiologia , Infecções por Salmonella/microbiologia , Epididimite/microbiologia , Orquite/diagnóstico , Orquite/terapia , Infecções por Salmonella/diagnóstico , Infecções por Salmonella/terapia , Drenagem , Salmonella enterica/isolamento & purificação , Epididimite/diagnóstico , Epididimite/terapia , Antibacterianos/uso terapêuticoRESUMO
The objective of this research was to identify brucellosis by Brucella abortus and the possible risk factors associated with the transmission of the infection in dogs in the urban area of the municipality of Viçosa-AL, as well as to alert health authorities about the risk of this potential zoonosis, create a booklet to alert the population about the risks of the disease and the possibility of creating a test protocol in clinical care at the Veterinary Hospital of the Federal University of Alagoas. A study was carried out in the city of Viçosa-AL to investigate the presence of B. abortus in 30 adult male dogs. The animals that showed symptoms suggestive of reproductive disease were referred for evaluation of the hematological pattern and clinical and surgical treatment. Parallel to the blood collection, a questionnaire was applied to the owners of these dogs. Buffered acid antigen (AAT) techniques were used as a screening test and 2-Mercaptoethanol (2-ME) as a confirmatory test for AAT positives with symptoms of brucellosis. The study aimed to analyze the number of positive dogs, the clinical and anatomopathological changes and the risk factors for the occurrence of brucellosis in dogs in the municipality of Viçosa-AL. As dogs are a means of transmission for humans, health authorities must pay special attention to this disease, including the control of dogs in the Program for Control and Eradication of Brucellosis of the Ministry of Agriculture. In addition to intensifying control of vaccination and diagnosis in cattle
O objetivo desta pesquisa foi identificar a brucelose por B. abortus e os possíveis fatores de risco associados à transmissão de infecção em cães na área urbana de Viçosa-AL, bem como alertar as autoridades de saúde sobre o risco dessa potencial zoonose, criar cartilha para alertar a população sobre os riscos da doença e a possibilidade de criação de um protocolo de teste no atendimento clínico do Hospital Veterinário da Universidade Federal de Alagoas. Um estudo foi realizado no município de Viçosa-AL para investigar a presença de B. abortus em 30 cães machos adultos. As técnicas do Antígeno Acidificado Tampado (AAT) foram usadas como teste de triagem e o 2-Mercaptoetanol (2-ME) como confirmatório dos positivos para AAT com sintomas de brucelose. Dos 30 animais testados com AAT, 15 eram domiciliados e 15 semi-domesticados, nos quais 60% (9/15) e 47% (7/15) desses cães eram reativos ao soro, respectivamente. Dos 16 cães reativos séricos para AAT, apenas 25% (4/16) apresentaram sintomas e foram testados com 2- ME, sendo confirmado 100% (4/4). Nos exames anatomopatológicos, foram observadas características típicas de animais brucélicos. Somente o contato com animais da fazenda foi associado à brucelose (p <0,05), sendo considerado fator de proteção
Assuntos
Animais , Masculino , Cães , Orquite/veterinária , Brucella abortus/isolamento & purificação , Brucelose/diagnóstico , Brucelose/epidemiologia , Mercaptoetanol , AntígenosRESUMO
BACKGROUND: Multi-organ damage is a common feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, going beyond the initially observed severe pneumonia. Evidence that the testis is also compromised is growing. OBJECTIVE: To describe the pathological findings in testes from fatal cases of COVID-19, including the detection of viral particles and antigens, and inflammatory cell subsets. MATERIALS AND METHODS: Postmortem testicular samples were obtained by percutaneous puncture from 11 deceased men and examined by reverse-transcription polymerase chain reaction (RT-PCR) for RNA detection and by light and electron microscopy (EM) for SARS-CoV-2. Immunohistochemistry (IHC) for the SARS-CoV-2 N-protein and lymphocytic and histiocytic markers was also performed. RESULTS: Eight patients had mild interstitial orchitis, composed mainly of CD68+ and TCD8+ cells. Fibrin thrombi were detected in five cases. All cases presented congestion, interstitial edema, thickening of the tubular basal membrane, decreased Leydig and Sertoli cells with reduced spermatogenesis, and strong expression of vascular cell adhesion molecule (VCAM) in vessels. IHC detected SARS-Cov-2 antigen in Leydig cells, Sertoli cells, spermatogonia, and fibroblasts in all cases. EM detected viral particles in the cytoplasm of fibroblasts, endothelium, Sertoli and Leydig cells, spermatids, and epithelial cells of the rete testis in four cases, while RT-PCR detected SARS-CoV-2 RNA in three cases. DISCUSSION AND CONCLUSION: The COVID-19-associated testicular lesion revealed a combination of orchitis, vascular changes, basal membrane thickening, Leydig and Sertoli cell scarcity, and reduced spermatogenesis associated with SARS-CoV-2 local infection that may impair hormonal function and fertility in men.
Assuntos
COVID-19/complicações , Orquite/patologia , Orquite/virologia , Testículo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2RESUMO
In context of COVID-19 pandemic, there has been different presentations of the infection. The relationship of testicular pain with COVID-19 has not been extensively studied. We present a 31 years old male, with SARS-COV-2 infection, repeatedly consulting for intermittent bilateral testicular pain. Two months later he reported acute loss sensibility and pain in extremities, being diagnosed with axonal fine fiber polyneuropathy. Although the presence of SARS-COV-2 in testis remains controversial, there is a potential orchiepididymitis risk due to viral binding to ACE2 receptor in testicle, and also could induce systemic vasculitis as another possible cause of orchitis.
RESUMO
Intravesical BCG therapy is effective in treating bladder cancer. Tuberculous epididymo-orchitis presents as a rare complication. There are very few cases described in which Mycobacterium Bovis produces epididymo-orchitis by itself.
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OBJECTIVE: This study investigated the effects of Tartrazine and Erythrosine (T+E) on the reproductive hormones and expression of some pro-inflammatory cytokines and testicular genes in testis of male Wistar rats. METHODS: 25 male Wistar rats (150-180g) were divided into 5 groups (n=5). Group 1 received distilled water while groups 2, 3, 4 and 5 were treated with T+E (2.5mg/kg, 5mg/kg, 10mg/kg and 20mg/kg) for the period of 23 days. Toxicity studies of the combined dye were investigated by evaluating serum reproductive hormones [Follicle stimulating hormone (FSH), Luteinizing hormone (LH), Testosterone], gene expression and profiling, and testes histology. RESULTS: male Wistar rats (150-180g) were divided into 5 groups (n=5). Group 1 received distilled water while groups 2, 3, 4 and 5 were treated with T+E (2.5mg/kg, 5mg/kg, 10mg/kg and 20mg/kg) for the period of 23 days. Toxicity studies of the combined dye were investigated by evaluating serum reproductive hormones [Follicle stimulating hormone (FSH), Luteinizing hormone (LH), Testosterone], gene expression and profiling, and testes histology. CONCLUSIONS: This present study reveals that the dyes could impair testicular function as evident in the up-regulation of pro-inflammatory cytokines and down-regulation of TESK-1 gene expression and architecture of the testes leading to Orchitis.
Assuntos
Hormônio Foliculoestimulante , Testículo , Animais , Corantes , Citocinas/genética , Regulação para Baixo , Expressão Gênica , Masculino , Proteínas Serina-Treonina Quinases , Ratos , Ratos Wistar , Receptores do FSH , Testículo/metabolismo , Regulação para CimaRESUMO
Experimental autoimmune orchitis (EAO) is a useful model to study organ-specific autoimmunity and chronic testicular inflammation. This model reflects testicular pathological changes reported in immunological infertility in men. Progression of EAO in rodents is associated with a significantly increased percentage of testicular endothelial cells and interstitial testicular blood vessels, indicating an ongoing angiogenic process. Vascular endothelial growth factor A (VEGFA), the main regulator of physiological and pathological angiogenesis, can stimulate endothelial cell proliferation, chemotaxis and vascular permeability. The aim of this study was to explore the role of VEGFA in the pathogenesis of testicular inflammation. Our results found VEGFA expression in Leydig cells, endothelial cells and macrophages in testis of rats with autoimmune orchitis. VEGFA level was significantly higher in testicular fluid and serum of rats at the end of the immunization period, preceding testicular damage. VEGF receptor (VEGFR) 1 is expressed mainly in testicular endothelial cells, whereas VEGFR2 was detected in germ cells and vascular smooth muscle cells. Both receptors were expressed in testicular interstitial cells. VEGFR2 increased after the immunization period in the testicular interstitium and VEGFR1 was downregulated in EAO testis. In-vivo-specific VEGFA inhibition by Bevacizumab prevented the increase in blood vessel number and reduced EAO incidence and severity. Our results unveil relevance of VEGFA-VEGFR axis during orchitis development, suggesting that VEGFA might be an early marker of testicular inflammation and Bevacizumab a therapeutic tool for treatment of testicular inflammation associated with subfertility and infertility.