Role of TNF-related apoptosis-inducing ligand (TRAIL) in the pathogenesis of varicocele-induced testicular dysfunction

Çelik, Orçun; Kutlu, Ömer; Tekcan, Merih; Çelik-Özenci, Çiler; Koksal, Ismail Turker

doi:10.1038/aja.2012.112

Cited by 20 publications

(16 citation statements)

References 29 publications

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“…The main pathophysiological consequence of testicular torsion is ischemia-reperfusion injury of the testis generated by the twisting of the spermatic cord which renders the tissue ischemic, and reperfusion occurs upon release of the twisted cord 9. Ischemia-reperfusion injury involves neutrophil recruitment; generation of reactive oxygen species (ROS), proinflammatory cytokines and adhesion molecules; lipid peroxidation; apoptosis; anoxia; and alteration of the microvascular blood flow, and it can result in infertility 1112…”

Section: Discussionmentioning

confidence: 99%

Comparison of intraperitoneal and intratesticular ozone therapy for the treatment of testicular ischemia-reperfusion injury in rats

et al. 2017

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We compare the efficacy of intratesticular ozone therapy with intraperitoneal ozone therapy in an experimental rat model. For this purpose, 24 rats were divided into four groups including sham-operated, torsion/detorsion, torsion/detorsion plus intraperitoneal ozone (O-IP), and torsion/detorsion plus intratesticular ozone (O-IT). The O-IP ozone group received a 4 mg kg−1 intraperitoneal injection of ozone, and the O-IT group received the same injection epididymally. At 4 h after detorsion, the rats were sacrificed and orchiectomy materials were assessed histopathologically. Spermatogenesis in the seminiferous tubules and damage to the Sertoli cells were histopathologically evaluated in the testes using the Johnsen scoring system. i-NOS and e-NOS activities in the testis tissue were also evaluated. Torsion-detorsion caused a decreased Johnsen score and increased apoptosis of spermatogonial and Sertoli cells. Ozone injection prevented increases in Johnsen score and i-NOS level. e-NOS level of the O-IP group was significantly lower than that of the O-IP group, and i-NOS level of the O-IT group was significantly lower than that of the O-IP group. Local ozone therapy is more effective than systemic ozone therapy at improving IRI-related testicular torsion. Our study is the first to show that the efficacy of intratesticular implementation of ozone therapy is higher than that of intraperitoneal ozone therapy.

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Section: Discussionmentioning

confidence: 99%

Comparison of intraperitoneal and intratesticular ozone therapy for the treatment of testicular ischemia-reperfusion injury in rats

et al. 2017

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“…In a study to investigate the role of TRAIL and its receptors in varicocele‐induced testicular dysfunction in an experimental rat model, Celik et al . () did not detect significant differences among the studied rat groups in term of TRAIL expression after varicocele induction. In contrast to the rat findings, results of the present study detected a significant increase in seminal TRAIL level in infertile patients with varicocele, pointing to a possible role of TRAIL in varicocele‐associated infertility in humans.…”

Section: Discussionmentioning

confidence: 63%

“…TNF‐related apoptosis‐inducing ligand and its receptors are expressed constitutively in a wide range of tissues including the testis (Grataroli et al ., , ; Celik et al ., ). In adult human testis, TRAIL and all its receptors were detected in postmeiotic germ cells.…”

Section: Introductionmentioning

confidence: 97%

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Seminal Tumour necrosis factor-related apoptosis-inducing ligand and its relationship to infertility in Egyptian patients with varicocele

Eid

Younan

2014

Andrologia

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Germ cell apoptosis has been proposed as one of the mechanisms by which varicocele can influence fertility. The aim of this study was to investigate the relationship between seminal tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) levels and male infertility in patients with varicocele. This study included 112 males: 30 fertile males with varicocele, 44 infertile males with varicocele and 38 healthy fertile control subjects without varicocele. Semen analysis was performed, and serum levels of reproductive hormones were measured. Seminal TRAIL levels in the infertile varicocele group were significantly higher than in the fertile varicocele and the control groups (P = 0.014). A significant negative correlation was found between seminal TRAIL and progressive (P < 0.001) and total motility scores (P < 0.001) in the infertile varicocele group. A significant negative correlation was also detected between seminal TRAIL levels and normal sperm morphology in the fertile varicocele (P = 0.007) and infertile varicocele patients (P = 0.047). Seminal TRAIL was significantly correlated with varicocele grade whether the patients were fertile (P = 0.001) or infertile (P = 0.035). Seminal TRAIL may thus have a potential role in varicocele-associated male infertility through its negative effect on sperm motility and morphology.

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“…Our pathway analysis for miRNA‐targeted genes in SCOS patients showed that largest number of genes were interconnected and associated with tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) pathway signaling, which is known to be involved in cell growth, differentiation, and apoptosis (Grataroli et al ., ; Falschlehner et al ., ). It is significant that receptors for this ligand coded by the TNFSF10 gene are found to be expressed in the testis (Grataroli et al ., , ; Celik et al ., ), and the activation of TRAIL signaling pathway in patients with testicular dysfunction is also indicated by the significant upregulation of TNFSF10 expression in SCOS patients in the GEO data set.…”

Section: Discussionmentioning

confidence: 94%

MicroRNA expression profiles in testicular biopsies of patients with impaired spermatogenesis

et al. 2016

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Spermatogenesis is a complex process that involves thousands of genes whose expression during different stages is strictly regulated. Small non-coding microRNAs play an important role in the posttranscriptional regulation of mRNA processing during spermatogenesis. Using Agilent SurePrint v16 microRNA 8 × 60 K microarray kit, we investigated the microRNA expression profiles of 24 formalin-fixed paraffin-embedded testicular biopsies from patients with hypospermatogenesis (n = 10), hypospermatogenesis and azoospermia factor c region on the Y chromosome (AZFc) deletion (n = 3), Sertoli cell-only syndrome (n = 3) and maturation arrest (n = 2), in comparison with subjects with normal spermatogenesis (n = 6). After adjusting for multiple testing, six deregulated miRNAs were detected in the patients with AZFc deletion, 30 in maturation arrest group, 52 in Sertoli cell-only syndrome group of patients, and none in the group of patients with hypospermatogenesis. Some of the deregulated microRNAs were shared between groups, resulting in 58 unique differentially expressed microRNAs. The expression of five microRNAs (hsa-miR-34b, hsa-miR-449b, hsa-miR-517c, hsa-miR-181c, and hsa-miR-605) was validated by qRT-PCR in a total of 74 samples. Using mRNA expression profiles of subjects with matching histopathological patterns of impaired spermatogenesis from publically available Gene Expression Omnibus data sets, we have performed integrated mRNA-microRNA regulatory network analysis. Pathway analysis revealed significantly enriched set of genes for tumor necrosis factor-related apoptosis-inducing ligand signaling pathway, previously shown to be involved in regulation of apoptosis in normal functioning testis. Our results should be considered as preliminary as we have analyzed only a small number of patients in each studied group. Further studies with larger number of patients with impaired spermatogenesis as well as more targeted approaches with parallel microRNA and mRNA expression profiling in isolated subpopulations of somatic or germ cells from different stages of spermatogenesis are needed to clarify the role of the microRNAs in the process of spermatogenesis.

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Role of TNF-related apoptosis-inducing ligand (TRAIL) in the pathogenesis of varicocele-induced testicular dysfunction

Cited by 20 publications

References 29 publications

Comparison of intraperitoneal and intratesticular ozone therapy for the treatment of testicular ischemia-reperfusion injury in rats

Comparison of intraperitoneal and intratesticular ozone therapy for the treatment of testicular ischemia-reperfusion injury in rats

Seminal Tumour necrosis factor-related apoptosis-inducing ligand and its relationship to infertility in Egyptian patients with varicocele

MicroRNA expression profiles in testicular biopsies of patients with impaired spermatogenesis

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