Characterization of varicocele-induced animal models: Potential role of inflammasome complex in the varicocele pathophysiology

Nogueira, Gustavo Augusto Keusch Albano; Maciel, Valter Luiz; Minas, Aram; Antoniassi, Mariana Pereira

doi:10.1016/j.jri.2021.103442

Cited by 8 publications

(7 citation statements)

References 78 publications

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“…The MPV used as an inflammation marker in varicocele condition, demonstrating changes in the platelet function, activation, and thrombocyte activity 28 . Also, increased pyrin domain‐containing protein 3 (NLRP3) expression levels in varicocele patients have been recently reported, which reveals this complex involvement in the maturation of pro‐caspase‐1, pro‐IL‐1β, and pro‐IL‐18 in seminal plasma of men with varicocele, 36 which is a key factor for the treatment 37 . In addition, cyclooxygenases (COXs) are enzymes involved in the conversion of polyunsaturated fatty acids and arachidonic acid to prostaglandins 38 .…”

Section: Evidence Of Inflammation Pathophysiology In Varicocelementioning

confidence: 96%

“…47 Also, due to the ethical limitation of using the testicular tissue of varicocele patients for investigation, animal models, especially rats, has been used repeatedly used as the best choice to investigate the inflammatory cells in the varicocele condition. 37 For example, Razi and colleagues investigated inflammatory cells in a time-dependent manner and revealed that the number of mononuclear immune cells (MNIs) increased in varicocele-induced rats. In addition, the number of MNIs increased in the testis was not only observed in the induced testis (left testis) but also in the right testicular tissue.…”

Section: Cytokine Production In Varicocele Testis and Epididymis (Ani...mentioning

confidence: 99%

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Insight into inflammation involvement in varicocele: A narrative review

Minas,

de Oliveira Rodrigues,

Camargo

et al. 2023

American J Rep Immunol

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BackgroundVaricocele is one of the main causes of male infertility. Although the pathophysiology mechanism of varicocele is very well described and understood, there are some unanswered questions that remains unknown. Some studies have previously described the state of testicular inflammation and sperm in animal models, especially the mouse model, and the seminal plasma of men with varicocele, with or without changes in semen parameters.Methods of studyThis review intended to verify the role of inflammatory mechanism in varicocele, using clinical studies as well as animal model studies on the effect of inflammation caused by varicocele on the function of testicular somatic and germ cells.ResultsIn‐vivo studies confirmed whether anti‐inflammatory molecules could treat the semen of men with varicocele and rats with varicocele. The use of different anti‐inflammatory agents in mouse model studies provided a new perspective for future clinical studies to investigate the effect of concurrent treatment with surgery to improve surgical outcomes.ConclusionSimilar to animal model studies, previously conducted clinical trials have demonstrated the effectiveness of anti‐inflammatory therapy in varicocele patients. However, clinical trials using anti‐inflammatory are needed to be conducted agents to evaluate different aspects of this therapeutical approach in varicocele patients.

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Section: Evidence Of Inflammation Pathophysiology In Varicocelementioning

confidence: 96%

Section: Cytokine Production In Varicocele Testis and Epididymis (Ani...mentioning

confidence: 99%

Insight into inflammation involvement in varicocele: A narrative review

Minas,

de Oliveira Rodrigues,

Camargo

et al. 2023

American J Rep Immunol

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“…The MAPK pathway's vital role in the phosphorylation of effector proteins and transcription proteins, such as nuclear factor‐kappaB (NF‐κB) in testis, has been revealed in various studies 73,74 . Indeed, active NF‐κB leads to pro‐inflammatory cytokine IL‐1β and IL‐18 expression in testis, 75 demonstrating TT promotes various cytokines expression through different pathways such as MAPK 76,77 . NF‐κB activation in the case of I/R condition, in TT‐induced testis, has been shown previously 78 .…”

Section: Tt‐induced Inflammation Impact On Testicular Tissue and Anti...mentioning

confidence: 99%

Testicular torsion in vivo models: Mechanisms and treatments

et al. 2023

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BackgroundTesticular torsion is a condition in which a testis rotates around its longitudinal axis and twists the spermatic cord. This in turn results in a significant decrease in blood flow and perfusion of testicular tissue. During Testicular torsion, the testicular tissue is affected by ischemia, heat stress, hypoxia, and oxidative and nitrosative stress. The testicular torsion should be considered an emergency condition and surgical intervention (testicular detorsion ) as the sole treatment option in viable cases involves counter‐rotation on twisted testes associated, when possible, to orchipexy, in order to avoid recurrence. Possible testicular detorsion side‐effects occur due to reperfusion and endothelial cells injury, microcirculation disturbances, and intense germ cells loss.ObjectivesTo discuss testicular torsion surgery‐based methods, different time frames for testicular torsion induction, and the associated pathophysiology by emphasizing cellular and molecular events as well as different therapeutic agent applications for testicular torsion.Materials and methodsWe reviewed all original research and epidemiological papers related to testicular torsion condition.ResultsTesticular torsion causes germ cell necrosis, arrested spermatogenesis, and diminished testosterone levels, with consequent infertility. Among different involved pathophysiological impacts, testicular torsion/detorsion‐induced ischemia seems to play the key role by leading the tissue toward other series of events in testis. Numerous studies have used adjuvant antioxidants, calcium channel blockers, anti‐inflammatory agents, or vasodilating agents in order to decrease these effects.Discussion and conclusionTo the best of our knowledge, no previously conducted study examined therapeutical agents' beneficial effects post clinical I/R condition in humans. Different agents targeting different pathophysiological conditions were used to ameliorate the ischemia/reperfusion‐induced condition in animal models, however, none of the administrated agents were tested in human cases. Although considering testicular detorsion surgery is still the golden method to reverse the testicular torsion condition and the surgical approach is undeniable, the evaluated agents with beneficial effects, need to be investigated furthermore in clinical conditions. Thus, furthermore clinical studies and case reports are required to approve the animal models proposed agents' beneficial impacts.

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“…There is an emergency growing body of evidence that suggests an association between male infertility induced by some diseases or medical conditions like varicocele, obesity and spinal cord injury. Varicocele has been reported to be responsible for 15% of total infertile men cases, while almost 40% of men with primary infertility, and more than 80% of men with secondary infertility suffer from varicocele 6,7 . Despite, all amount of data presented in the literature, varicocele‐induced infertility's main pathophysiology remains unclear 8 .…”

Section: Introductionmentioning

confidence: 99%

“…18 Although inflammasome complexes have been studied during the last decades, the inflammasome complex participation in male infertility has gained attention recently. Regarding this issue, during the last 2 years, de Rivero Vaccari in 2020, 19 Tavalaee et al in 2022 20 and our group 7 reviewed different aspects of inflammasome complex participation in male and female infertility. However, considering the inflammasome complex's high potential to be targeted for drug therapy and complexity involvement in human reproduction, this study tries to shed light on current literature by focusing only on the male reproductive system and discussing the inflammasome complex activation in a disease-based manner.…”

mentioning

confidence: 99%

Insight toward inflammasome complex contribution to male infertility

Minas

Costa

Miyazaki

et al. 2023

American J Rep Immunol

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During the last decades, a wide range of factors involved in the physiopathology of male infertility disease have been discussed. The inflammation role in some of the main infertility-related diseases has been studied, such as varicocele, spinal cord injury and obesity. Inflammation is the main response of the immune system to infection or cell damage, leading to intense inflammatory cytokine release during the loss of homeostasis. One of the first steps toward pro-inflammatory cytokines release is the recognition of dangerous signals by the immune cells, including pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).These molecules can activate an important multiprotein complex, called inflammasome. Although these complexes have been studied during the last decades, their participation in male infertility has gained attention recently. Considering the inflammasome complex's high potential to be targeted for drug therapy, this review tries to shed light on current literature. Therefore, in the current review paper, we aimed to discuss the inflammasome complex activation, involvement in different male infertility conditions, and localization in the male reproductive tract.

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Characterization of varicocele-induced animal models: Potential role of inflammasome complex in the varicocele pathophysiology

Cited by 8 publications

References 78 publications

Insight into inflammation involvement in varicocele: A narrative review

Insight into inflammation involvement in varicocele: A narrative review

Testicular torsion in vivo models: Mechanisms and treatments

Insight toward inflammasome complex contribution to male infertility

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