testicular inflammation
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2021 ◽  
Vol 12 ◽  
Author(s):  
Tengyu Zhu ◽  
Xue Chen ◽  
Huan Qiu ◽  
Yang Liu ◽  
James Mwangi ◽  
...  

As an important source of air pollutant, airborne particulate matter (PM) has become a major threat to public health. Orchitis is characterized by acute or chronic testicular inflammation and is a primary cause of male infertility. Although accumulating evidence indicates that PM exposure is associated with increased male infertility rates, the mechanism by which PM is involved is not well understood. Here, we found that short-term PM exposure activated NF-κB signaling in mouse Leydig cells and testes and leading to asymptomatic orchitis. Analyzing the mitochondrial abundance and cGAMP levels in PM exposed mouse Leydig cells, we found that PM exposure induced mitochondrial injury and mtDNA release, leading to inflammation via the cGAS-STING axis. We also found that aspirin-induced acetylation of cGAS inhibited the inflammation in mice after PM exposure, especially in the testes. Moreover, aspirin pretreatment rescued offspring growth in PM-exposed mice. In summary, our study not only provides evidence that PM-induced asymptomatic orchitis in mice may be amenable to aspirin pre-treatment by acetylating cGAS, but also provides a potential explanation for male infertility caused by air pollutants.


Author(s):  
Ruifeng Zeng ◽  
Chengli Jin ◽  
Chuchu Zheng ◽  
Shaoqi Li ◽  
Siyue Qian ◽  
...  

Octamer-binding transcription factor 4 (OCT4) and cancerous inhibitor of protein phosphatase 2A (CIP2A) are upregulated in testicular cancer and cell lines. However, its contribution to orchitis (testicular inflammation) is unclear and was thus, investigated herein. Cell-based experiments on a lipopolysaccharide (LPS)-induced orchitis mouse model revealed robust inflammation, apoptotic cell death, and redox disorder in the Leydig (interstitial), Sertoli (supporting), and, germ cells. Meanwhile, real-time quantitative PCR revealed low OCT4 and CIP2A levels in testicular tissue and LPS-stimulated cells. A gain-of-function study showed that OCT4 overexpression not only increased CIP2A expression but also repressed LPS-induced inflammation, apoptosis, and redox disorder in the aforementioned cells. Furthermore, the re-inhibition of CIP2A expression by TD-19 in OCT4-overexpressing cells counteracted the effects of OCT4 overexpression on inflammation, apoptosis, and redox equilibrium. In addition, our results indicated that the Keap1-Nrf2-HO-1 signaling pathway was mediated by OCT4 and CIP2A. These findings provide insights into the potential mechanism underlying OCT4- and CIP2A-mediated testicular inflammation.


2020 ◽  
Vol 11 (6) ◽  
pp. 71-78
Author(s):  
Dmitry O. Ivanov ◽  
Vladimir N. Timchenko ◽  
Lyubov M. Pochinyaeva ◽  
Maria A. Shakmaeva ◽  
Tatyana A. Kaplina ◽  
...  

Mumps currently is a vaccine-preventable infections. However, mumps still remains an urgent problem all over the world, due to periodic increases in the incidence in older children (including the vaccinated ones against this infection), in adults (the disease often does not go smoothly with involving various organs in the pathological process and systems). The literature describes the various adverse effects of male mumps, including infertility, testicular atrophy, testicular tumors, impotence, gynecomastia, etc. The article provides information on the incidence of mumps in the Russian Federation and St. Petersburg, the clinical manifestation of the infection. It was noted that in adolescent boys and men, the presence of orchitis (orchoepididymitis) is a frequent symptom of the disease. It is shown in the article, that testicular inflammation rate increases with age of patients. A brief description of modern methods of laboratory diagnostics and therapy is given in accordance with clinical recommendations and treatment standards. A clinical case of mumps, combined severe form (mumps + orchoepididymitis), in a 17-year-old boy is presented in this article. The features of the course of the disease, the results of laboratory and instrumental examination and treatment have been analyzed in this item. Conservative therapy (antiviral and antibacterial) of mumps, as well as timely surgical treatment of orchoepididymitis, led to a complete clinical and laboratory recovery of the patient.


Author(s):  
Gisela Soledad Gualdoni ◽  
Patricia Verónica Jacobo ◽  
Cristian Marcelo Sobarzo ◽  
Cecilia Valeria Pérez ◽  
Luis Alberto Haro Durand ◽  
...  

Abstract 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.


2020 ◽  
Vol 11 ◽  
Author(s):  
Livia Lustig ◽  
Vanesa A. Guazzone ◽  
María S. Theas ◽  
Christiane Pleuger ◽  
Patricia Jacobo ◽  
...  

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Shobana Navaneethabalakrishnan ◽  
Bethany L Goodlett ◽  
Brett M Mitchell

Hypertension (HTN) is associated with reduced fertility in men. Although numerous studies report that HTN disrupts hormonal balance in men, less is known about the direct effect of HTN on testes and how HTN influences testicular inflammation and lymphatics. We hypothesized that HTN increases testicular lymphatic vessel density and this is associated with immune cell infiltration and inflammation. Male mice (8 weeks old) were made hypertensive by providing them with L-arginine methyl ester hydrochloride (L-NAME) (0.5 mg/mL) in the drinking water for 3 weeks and control mice received tap water. Testes of hypertensive mice had a significant increase in gene expression of the lymphatic vessel markers Lyve-1 (17.7 ± 2.1 fold; p<0.05), Podoplanin (6.7 ± 1.2 fold; p<0.05), and Prox-1 (68.1 ± 10.6 fold; p<0.05), the lymphangiogenic growth factors VEGF-C (5.7 ± 1.1 fold; p<0.05), VEGF-D (2.2 ± 0.7 fold; p<0.05), and VEGF-A (5.8 ± 1.1 fold; p<0.05) and their receptors VEGFR-2 (8.0 ± 2.0 fold; p<0.05) and VEGFR-3 (25.4 ± 3.5 fold; p<0.05). There was also a significant increase in the expression of the pro-inflammatory cytokines TNF-a (24.0 ± 6.8 fold; p<0.05), IFN-g (17.5 ± 3.0 fold; p<0.05), IL-1b (4.2 ± 1.2 fold; p<0.05), IL-6 (24.8 ± 13.0 fold; p<0.05), and IL-17 (4.4 ± 0.4 fold; p<0.05). There were also increases in the lymphatic endothelial cell-derived immune cell trafficking chemokines CCL21 (7.8 ± 1.7 fold; p<0.05) and CCL19 (9.0 ± 4.1 fold; p<0.05) and their receptor CCR7 (9.6 ± 3.2 fold; p<0.05), as well as the cell adhesion molecule ICAM (6.2 ± 1.0 fold; p<0.05) in testes of hypertensive mice. Flow cytometry analysis revealed an increased accumulation of F4/80+ macrophages in the testes from hypertensive mice. Together, these data demonstrate that HTN induces inflammation-associated lymphangiogenesis in testes, in association with immune cell infiltration. It is possible that increasing testicular lymphatics may reduce inflammation and improve reproductive function in hypertensive men.


2020 ◽  
Vol 84 (3) ◽  
Author(s):  
Emily R. Bryan ◽  
Jay Kim ◽  
Kenneth W. Beagley ◽  
Alison J. Carey

2019 ◽  
Author(s):  
Ross Gillette ◽  
Richa Tiwary ◽  
Jorine JLP Voss ◽  
Shavini N Hewage ◽  
John H Richburg

AbstractPeripubertal exposure to the phthalate metabolite mono-(2-ethylhexyl) phthalate (MEHP) in rodents causes testicular inflammation, spermatocyte apoptosis, and disruption of the blood-testis barrier. The MEHP-induced inflammation response includes an infiltration of macrophages and neutrophils to the testes, although the cause and purpose of this response is unknown. Recently, a population of testicular macrophages phenotypically distinct from those resident in the interstitium was described in mice. Testicular peritubular macrophages aggregate near the spermatogonial stem cell niche and are believed to stimulate their differentiation. We hypothesized that if testicular peritubular macrophages do indeed stimulate spermatogonial differentiation, MEHP exposure would result in an increase of peritubular macrophages to stimulate the replacement of lost spermatocytes. Male rats were exposed to 700 mg/kg MEHP or corn oil (vehicle control) via oral gavage at PND 28 and euthanized at 48 hours, 1 week, or 2 weeks later. Tubules were stained with immunofluorescent markers for macrophages and undifferentiated spermatogonia. Peritubular macrophages were observed in rat testis similar to those previously described in mice: MHC-II+ cells on the surface of seminiferous tubules with heterogeneous morphology. Quantification of MHC-II+ cells revealed that, unlike in the mouse, their numbers did not increase through puberty. MEHP increased macrophage presence by six-fold 48-hours after exposure and remained elevated by two-fold two weeks after exposure. An increase of differentiating spermatogonia occurred two weeks after MEHP exposure. Taken together, our results suggest that peritubular macrophages play a crucial role in the testis response to acute injury and the subsequent recovery of spermatogenesis.Summary SentencePhthalate-induced testicular injury results in an increase of specialized peritubular macrophages that may assist in the recovery of spermatogenesis.


2019 ◽  
Vol 46 (6) ◽  
pp. 5983-5994 ◽  
Author(s):  
Chioma Y. Ezirim ◽  
Sunny O. Abarikwu ◽  
Augustine A. Uwakwe ◽  
Chidimma J. Mgbudom-Okah

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