Search

Testicular torsion is an urological emergency and can lead to ischemia damage and testicular loss if not diagnosed in time. Proanthocyanidin is reported to have anti-inflammatory and antioxidant properties. The current study aimed to examine the possible effects of proanthocyanidin (P) on the testis in torsion/detorsion (T/D)-induced testicular ischemia/reperfusion (I/R) injury in rats. Forty rats were divided into four groups (n=10 for each): sham-operated (sham), I/R, I/R + P100 (100 mg/kg, 30 min before torsion), and I/R + P200 (200 mg/kg, 30 min before torsion). Testicular T/D was performed on the left testicle by 3 hours of torsion at 720° clockwise, followed by 3 hours of detorsion. In the I/R group, an increase in malondialdehyde (MDA) levels and a decrease in glutathione (GSH), vitamin C (Vit C), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD) values were determined compared to the sham group (p<0.001). Moreover, an increase in the expression of cleaved caspase-3 and Bcl2-associated X protein (Bax), a decrease in the expression of B-cell lymphoma 2 (Bcl-2) and proliferating cell nuclear antigen (PCNA) were detected in the I/R group (p<0.001). Histopathologically, it was determined that the Johnsen and Cosentino scores of the testicles were irregular in the I/R group (p<0.001). Proanthocyanidin treatment caused a decrease in MDA, cleaved caspase-3 and Bax levels and an increase in GSH, Vit C, GPx, G6PD, Bcl-2 and PCNA values. Additionally, Johnsen and Cosentino rearranged the scores. The present findings revealed the protective and curative effects of proanthocyanidin in organ damage due to testicular torsion/detorsion-induced ischemia/reperfusion with their antioxidative and antiapoptotic properties., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Cryptorchidism and testicular torsion (TT) are relatively common conditions in clinical practice; however, sparse information about cryptorchid TT is available in the current literature., Methods: We retrospectively reviewed the clinical characteristics, treatment modalities, and long-term outcomes of pediatric patients treated for acute cryptorchid TT., Results: We found eight patients with unilateral acute cryptorchid TT with a prevalence of 8.9% (8/90) among all TT cases. The left testis was affected in six patients. The median age of patients at the time of the surgery was 65 months (interquartile range (IQR) 4-136 months). The median duration of symptoms was 16 h (IQR 9-25 h), while the median time to treatment was 60 min (IQR 59-63 min). The most common symptoms were pain (abdominal and inguinal) and inguinal mass with no palpable testis in the ipsilateral hemiscrotum. Preoperative color Doppler ultrasonography revealed absent or decreased testicular blood flow in the affected testes in 7/8 of patients. Various degrees of testicular torsion (median 540°, min 360°, max 1260°) were found during surgery. A necrotic testis that led to orchidectomy was found in 4/8 of patients. The median follow-up period was 42.6 months (IQR 12.5-71.2 months), revealing only one patient with testicular atrophy. The final testicular salvage rate was 35%., Conclusions: Greater awareness among caregivers and primary care physicians about acute cryptorchid TT is required to improve their timely diagnosis and treatment. A physical examination of the external genitalia and inguinal regions should be mandatory to attain a proper diagnosis and treatment without delay., Competing Interests: Declaration of competing interest Una Glamoclija is an employee of Bosnalijek d.d., Sarajevo. Other authors do not have a conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: Tempol, a synthetic antioxidant compound, has received significant attention for its potential therapeutic applications in recent years, especially against ischemia/reperfusion (I/R) injury. The aim of the present research was to assess the protective effects of Tempol on testicular I/R injury caused by testicular torsion and detorsion (T/D) in rats., Methods: The subjects were divided into five groups: sham, testicular T/D, testicular T/D with Tempol treatment at 50 and 100 mg/kg, and healthy rats treated with Tempol at 100 mg/kg. Testicular torsion was induced by rotating the left testicles for 2 h, followed by detorsion for 24 h. Testicular tissues were evaluated for gene expression, oxidative stress markers, and histopathology, epididymal sperms were stained and analyzed, and blood serum samples were collected to measure the testosterone hormone., Results: The results showed that testicular I/R caused a significant decrease in sperm velocity parameters, viability, and count, as well as an increase in abnormal sperms (p < 0.05). However, treatment with Tempol significantly improved these parameters (p < 0.05). Histopathological analysis revealed severe damage to the testicular tissues, but treatment with Tempol improved the structural integrity of the seminiferous tubules. Testicular I/R also resulted in increased oxidative stress index and decreased testosterone levels significantly (p < 0.05), but Tempol administration mitigated these effects significantly (p < 0.05). Furthermore, the expression of Bax and Bcl 2 , genes associated with apoptosis, were significantly altered by testicular I/R (p < 0.05), but Tempol prevented these changes significantly (p < 0.05)., Conclusion: These findings provide strong evidence that Tempol can effectively prevent testicular I/R injury., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Aims: The aim of this study was to investigate the potential antioxidant, anti-inflammatory, and sperm function-preserving properties of sodium acetate (ACE), a histone deacetylase (HDAC) inhibitor, in a rat model of testicular torsion/detorsion (T/D)., Main Methods: Littermate Wistar rats of identical weight were subjected to sham surgery or testicular T/D by rotating the left testis at 720° around its axis along the spermatic cord clockwise and fixing it in this position for two and a half hours. 1 h before detorsion, T/D + ACE-treated rats were treated with ACE (200 mg/kg/day, per os) while T/D rats were vehicle-treated by administering 0.5 mL of distilled water. After 72 h, animals were euthanized, and the left testes were harvested for bio-molecular and histological analysis., Key Findings: Acetate administration attenuated T/D-induced rises in serum and testicular HDAC and testicular xanthine oxidase, uric acid, MDA, GSSG, MPO, TNF-α, IL-1β, IL-6, NFkB, HIF-1α, and VCAM-1. In addition, acetate treatment alleviated T/D-induced decline in sperm quality (count, motility, viability, and normal morphology) and testicular 3β-HSD, 17β-HSD, testosterone, GSH, GSH/GSSG, SOD, catalase, GPx, GST, Nrf2, and HO-1. Furthermore, acetate prevented T/D-distorted testicular histoarchitecture and spermatogenic germ cell loss., Significance: Sodium acetate during the post-ischaemic phase of testicular T/D may be beneficial in preventing I/R injury and maintaining fertility., Competing Interests: Declaration of competing interest Authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

The present study aimed to investigate the effects of Phoenixin-14 (PNX-14) on oxidative damage, inflammatory response, histopathological variations, and serum testosterone levels in testicular tissues. Forty-eight Wistar albino prepubertal male rats were divided into 4 groups (Sham, TTD, TT+PNX+TD, TTD+PNX) (n=12). The torsion period was 2 hours and the detorsion period was 24 hours in the testicular torsion/detorsion (TD) groups. A single PNX-14 (50 µg/kg) dose was injected into the rats in the TT+PNX TD group on the 90th minute of torsion, and it was injected into the rats in the TTD+PNX group at the beginning of detorsion. Oxidative damage in testicular tissues was determined based on superoxide dismutase (SOD), malondialdehyde (MDA), total antioxidant status (TAS) and total oxidant status (TOS), and inflammatory damage was determined based on TNF-α and IL-6 levels. Histopathological variations were investigated with the Periodic Acid Schiff (PAS) staining method in testicular tissues and analyzed based on Johnsen scores. Spermatogonia cells were examined immunohistochemically. Serum testosterone levels were determined with the enzyme-linked immunosorbent assay (ELISA). A significant increase in oxidative stress and inflammation parameters was determined in the TTD group when compared to the other groups (p<0.05). PNX-14 treatment led to a statistically significant decrease in these parameters and significantly repaired the TD damage in testicular tissue (p<0.05). Johnsen scoring revealed significant improvement in PNX-14 groups and an increase in spermatogonia count, supporting the biochemical findings (p<0.05). PNX-14 could be a potential therapeutic agent in testicular TD damage and further studies should be conducted to elucidate the present study findings., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Testicular torsion carries the ominous prospect of inducing acute scrotal distress and the perilous consequence of testicular atrophy, necessitating immediate surgical intervention to reinstate vital testicular perfusion, notwithstanding the paradoxical detrimental impact of reperfusion. Although no drugs have secured approval for this urgent circumstance, antioxidants emerge as promising candidates. This study aspires to illustrate the influence of eprosartan, an AT1R antagonist, on testicular torsion in rats. Wistar albino rats were meticulously separated into five groups, (n = 6): sham group, eprosartan group, testicular torsion-detorsion (T/D) group, and two groups of T/D treated with two oral doses of eprosartan (30 or 60 mg/kg). Serum testosterone, sperm analysis and histopathological examination were done to evaluate spermatogenesis. Oxidative stress markers were assessed. Bax, BCL-2, SIRT1, Nrf2, HO-1 besides cleaved caspase-3 testicular contents were estimated using ELISA or qRT-PCR. As autophagy markers, SQSTM-1/p62, Beclin-1, mTOR and AMPK were investigated. Our findings highlight that eprosartan effectively improved serum testosterone levels, testicular weight, and sperm count/motility/viability, while mitigating histological irregularities and sperm abnormalities induced by T/D. This recovery in testicular function was underpinned by the activation of the cytoprotective SIRT1/Nrf2/HO-1 axis, which curtailed testicular oxidative stress, indicated by lowering the MDA content and increasing GSH content. In terms of apoptosis, eprosartan effectively countered apoptotic processes by decreasing cleaved caspase-3 content, suppressing Bax and stimulating Bcl-2 gene expression. Simultaneously, it reactivated impaired autophagy by increasing Beclin-1 expression, decreasing the expression of SQSTM-1/p62 and modulate the phosphorylation of AMPK and mTOR proteins. Eprosartan hold promise for managing testicular dysfunction arising from testicular torsion exerting antioxidant, pro-autophagic and anti-apoptotic effect via the activation of SIRT1/Nrf2/HO-1 as well as Beclin-1/AMPK/mTOR pathways., (© 2024. The Author(s).)

Objective: Testicular ischemia-reperfusion induced by testicular torsion-detorsion increases the level of reactive oxygen species, leading to testicular damage. Allicin, one of the most active ingredients in garlic, is a significant exogenous antioxidant. In the research, the efficacy of allicin in treating testicular ischemia-reperfusion injury was assessed., Materials and Methods: The study included sixty Sprague-Dawley male rats. Three groups with 20 rats per group were created as follows: control group, testicular ischemia/reperfusion-induced group, and testicular ischemia-reperfusion plus treatment with allicin group. The control group underwent a sham operation of the left testis without other interventions. In the testicular ischemia/reperfusion-induced group, rat left testis was subjected to 720° torsion for two hours and then detorsion. In the allicin-treated group, in addition to testicular ischemia-reperfusion, 50 mg/kg of allicin was injected intraperitoneally, starting immediately following detorsion. Testicular tissue samples were obtained to measure the protein expression of xanthine oxidase, which is a major source of reactive oxygen species formation, malondialdehyde level (a reliable marker of reactive oxygen species), and testicular spermatogenic function., Results: Testicular ischemia-reperfusion significantly increased the expression of xanthine oxidase and malondialdehyde levels in ipsilateral testes while reducing testicular spermatogenic function. The expression of xanthine oxidase and malondialdehyde levels were significantly lower in ipsilateral testes, whereas testicular spermatogenic function in the allicin-treated group was significantly higher compared with those in the testicular ischemia-reperfusion group., Conclusions: Our findings indicate that allicin administration improves ischemia/reperfusion-induced testicular damage by limiting reactive oxygen species generation via inhibition of xanthine oxidase expression.

Introduction: The testicular ischemia-reperfusion (I/R) injury is characterized by the excessive aggregation of un-scavenged reactive oxygen species, leading to the heightened levels of oxidative stress. This phenomenon plays a pivotal role in the pathophysiology of testicular torsion damage., Objective: The current study aimed to detect the prophylactic and therapeutic effects of niacin on testicular I/R injury., Study Design: Twenty-four healthy adult male Sprague Dawley rats were randomly allocated into three groups as follows: (1) sham group, (2) torsion/detorsion (T/D) group, and (3) treatment group which received 200 mg/kg niacin along with testicular T/D. Torsion/detorsion was induced by 2 h of torsion followed by 10 days of reperfusion period. In the treatment group, niacin was injected 30 min before the reperfusion period intraperitoneally and continued for 10 days by oral gavage., Results: T/D was associated with marked decreases in terms of sperm count, viability, and kinematic parameters versus the sham group (P < 0.05), which niacin significantly reverted the kinematic parameters (P < 0.05). I/R injury caused a significant increase in the number of abnormal epididymal sperms compared to the sham group (P < 0.05). Niacin decreased the epididymal sperm abnormality significantly compared to the T/D group (P < 0.05). Tissue abnormalities in T/D group, such as edema, hyperemia, inflammation, and necrosis were completely visible histopathologically, while the histological changes in the niacin-treated group were better than those in the T/D group. Regarding the pathological parametric evaluations, I/R injury significantly reduced the mean testicular biopsy score (MTBS), germinal epithelial cell thickness (GECT), and mean seminiferous tubular diameter (MSTD), and increased the tubular hypoplasia/atrophy (THA) compared to the sham group (P < 0.05), which niacin treatment significantly improved the MTBS and GECT compared to the T/D group (P < 0.05). T/D significantly increased the oxidative stress index (OSI) and lipid peroxidation (MDA) (P < 0.05). Niacin significantly reduced the OSI and MDA levels compared to the T/D group (P < 0.05)., Discussion: The current study found that niacin has preventive/therapeutic effects against the elevation of oxidative stress markers and depletion of antioxidants during I/R injury. Following administration of niacin, a reduction in histologic injury was observed in rats. In our study, we showed the antioxidant properties of niacin and its capacity to protect against I/R damage., Conclusion: The findings of the present investigation revealed that niacin, as an antioxidant agent, can suppress the oxidative stress induced by testicular I/R injury, and can be used as a supplementary agent in the treatment of those undergoing testicular torsion surgery., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2024 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background/aims: Ischemic reperfusion (I-R) injury is greatly influenced by the testicular torsion/detorsion process (TDP). In this instance, the anti-inflammatory properties of plateletrich plasma (PRP) combined with tadalafil (Td) significantly promote tissue healing in the I-R injury model., Methods: Five groups of rats were created: the control group, the I-R group not receiving any therapy, the I-R group receiving a single dosage of Td (0.25 mg/kg, I.P.), the I-R group receiving a single dose of PRP (80 l, intratesticular), and the I-R group receiving both Td and PRP. Sperm morphology, motility, and histology were assessed. The levels of TNF-, BAX, antioxidant status, and testosterone were measured. Additionally, E-selectin expression was done., Results: PRP reduced oxidative stress, inflammation, and apoptosis while also boosting testosterone levels, which alleviated I-R injury. Otherwise, PRP reduces E-selectin expression, which modifies the pathways that control endothelial function. Td also partially demonstrated its testicular-protective activity at the same time., Conclusion: PRP's proven anti-inflammatory, antioxidant, and antiapoptotic potentials make it a natural treatment for testicular harm caused by tadalafil. For the first time, it was demonstrated that PRP therapy restored the functionality of the vascular endothelium, specifically the control of E-selectin expression. Combining Td and PRP therapy may be a promising strategy for improving response to PDE5 inhibitors., Competing Interests: The authors have no conflicts of interest to declare., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Objective: The current study aimed to explore the potential protective effect of Passiflora Incarnata L., (PI) in treating IR injury after testicular torsion in rats., Materials and Methods: This research investigated the impact of PI on IR damage in male Wistar albino rats. Animals were divided to three groups: group 1 (sham), group 2 (IR), and group 3 (IR+PI)., Results: The malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) levels did not significantly differ across the groups (p = 0.830, p = 0.153 and p=0.140, respectively). However, Group 3 demonstrated a superior total antioxidant status (TAS) value compared to Group 2 (p = 0.020). Concurrently, Group 3 presented a significantly diminished mean total oxidant status (TOS) relative to Group 2 (p = 0.009). Furthermore, Group 3 showed a markedly improved Johnsen score relative to Group 2 (p < 0.01). IR caused cell degeneration, apoptosis, and fibrosis in testicular tissues. PI treatment, however, mitigated these effects, preserved seminiferous tubule integrity and promoted regular spermatogenesis. Furthermore, it reduced expression of tumor necrosis factor-alpha (TNF-α), Bax, and Annexin V, signifying diminished inflammation and apoptosis, thereby supporting cell survival (p < 0.01, p < 0.01, p < 0.01, respectively)., Conclusions: This study revealed that PI significantly reduces oxidative stress and testicular damage, potentially benefiting therapies for IR injuries., (Copyright: © 2024 Permanyer.)

Purpose: Cut-off time to avoid orchiectomy relies on small series of patients. The objective was to determine the cut-off time to avoid orchiectomy in torsion of the spermatic cord in a large cohort., Methods: We performed a retrospective multicenter study (TORSAFUF cohort) of patients with suspected spermatic cord torsion between 2005 and 2019. All patients aged > 12 years who were suspected of having a torsion of the spermatic cord in 14 University Hospitals in France were included (n = 2986). Patients for whom data on pain duration were not available (n = 923) or for whom the final diagnosis was not torsion of the spermatic cord (n = 807) were excluded. The primary outcome was orchiectomy. The secondary outcomes were testicular survival time and the prediction of orchiectomy with the duration of pain., Results: 1266 patients were included with an orchiectomy rate of 12% (150 patients). The mean age was 21.5 years old in the salvage group and 23.7 years old in the orchiectomy group (p = 0.01), respectively. The median time from the onset of pain to surgery was 5.5 (IQR = 5) hours in the salvage group and 51.1 (IQR = 70) hours in the orchiectomy group (p < 0.0001). The risk of orchiectomy increased after a time cut-off of 6 h 30. A delay of 15 h 30 in pain duration was found to predict orchiectomy (sensitivity: 0.81; specificity: 0.87)., Conclusions: Pain duration can predict the probability of salvaging the testicles and performing orchiectomy. Rapid intervention should be recommended, regardless of the time elapsed from the onset of pain., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Testicular torsion is a urological emergency. However, surgical detorsion of the torsed spermatic cord can cause testicular reperfusion injury. Although remote ischemic preconditioning (RIPC) has been convincingly shown to protect organs against ischemia/reperfusion (I/R) injury, little is known regarding the effect of RIPC on testicular torsion/detorsion-induced reperfusion injury. Therefore, we aimed to evaluate the effect of RIPC on testes after testicular I/R injury in a rat model in vivo. Male Sprague-Dawley rats were randomly classified into 4 groups: sham-operated (sham), testicular I/R (TI/R), or remote liver (RIPC liver) and limb (RIPC limb) ischemic preconditioning groups. Testis I/R was induced by 3 h of right spermatic cord torsion (720° clockwise), and reperfusion was allowed for 3 hours. In the RIPC group, four cycles of 5 min of ischemia and 5 min of reperfusion were completed 30 min prior to testicular torsion. The ERK1/2 inhibitor U0126 was administered intravenously at the beginning of reperfusion (1 mg/kg). The testes were taken for the oxidative stress evaluations, histology, apoptosis, immunohistochemical and western blotting analysis. Remote liver and limb ischemic preconditioning attenuated ipsilateral and contralateral testicular damage after testicular I/R injury. For example. RIPC reduced testicular swelling and oxidative stress, lessened structural damage, and inhibited the testicular inflammatory response and apoptosis. Furthermore, RIPC treatment enhanced testicular ERK1/2 phosphorylation postI/R. Inhibition of ERK1/2 activity using U0126 eliminated the protection offered by RIPC. Our data demonstrate for the first time that RIPC protects testes against testicular I/R injury via activation of the ERK1/2 signaling pathway., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Testicular and scrotal abnormalities can occur in children, adolescents, and adults. The lesions, often accompanied by pain and swelling/enlargement of the scrotum, can cause anxiety in patients and their parents. Regardless of age, proper diagnosis is based on adequate anamnesis and physical examination. Color Doppler ultrasound is the first-line test in the differential process of testicular and scrotal diseases. Testicular and scrotal lesions require differentiation for benign and malignant processes as well as therapeutic management, including urgent surgical intervention. The aim of this paper is to present the most common causes of testicular and scrotal abnormalities in pediatric and adult patients and to outline the symptoms and diagnostic and therapeutic management.

Objective: To evaluate the role of emergency manual detorsion as first line management for testicular torsion in the context of the COVID-19 pandemic., Methods: This retrospective observational study includes 90 pediatric patients ≤14 years old with diagnosis of testicular torsion made at 2 tertiary centers between October 2020 and June 2022. Variables examined included age, presentation delay, surgical wait time, number of attempts at manual testicular detorsion, and manual testicular detorsion success. All patients finally underwent surgery, including contralateral testicular fixation. Outcomes included predictors of successful manual detorsion, testicular findings at surgery, and operation time., Results: Mean (SD) age at diagnosis was 11.51 (2.64) years. Mean presentation delay was 11.76 (13.79) hours. Detorsion was attempted in 72 (80%) patients, resulting successful in 58 (80.5%). Surgical wait time after successful manual detorsion was 22.85 (16.94) hours. On multivariable analysis, successful manual detorsion was associated with a presentation delay<6 hours (odds ratios [OR] 0.154, 95% confidence intervals (CI) 0.036-0.655, P = 0.01) and absence of scrotal edema (OR 0.171, 95% CI 0.038-0.769, P = 0.02). Vice versa, a heterogeneous echo-texture (OR 0.57, 95% CI 0.007-0.461, P = 0.007) and absent blood flow on Doppler ultrasound scan (OR 0.256, 95% CI 0.067-0.971, P = 0.045) were significantly associated with the likelihood of manual detorsion failure., Conclusion: In our experience, manual detorsion provided safe and effective emergency treatment for pediatric testicular torsion, especially in absence of edema and when presentation delay is <6 hours. This maneuver should be more widely attempted immediately after diagnosis as temporizing rescue., Competing Interests: Declaration of Competing Interest 1) Tiziana Russo no conflict, 2) Denis A. Cozzi no conflict, 3) Giovanni Gaglione no conflict, 4) Silvia Ceccanti no conflict. I accept the responsibility for the completion of this document and attest to its validity on behalf of the co-authors., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Factors associated with testicular torsion (TT) and consequent orchiectomy in patients presenting to pediatric emergency departments (PEDs) with scrotal pain (SP) are not well described. We report the factors predicting TT and consequent orchiectomy in children with SP., Methods: The data on patients (aged ≤18 years) who presented with SP to PEDs at 4 branches of the Chang Gung Hospital through 10 years were analyzed., Results: In all, 256 pediatric patients presented with SP. Their mean age was 11.60 ± 4.61 years and 72.7% (n = 186) were aged 10 to 18 years. The pain was left-sided in 54.7% (n = 140) and the interval between SP onset and PED arrival was 22.45 ± 31.27 hours. Overall, 84 (32.8%) patients needed surgery and 72 (28.1%) had TT. Of the patients with TT, 28 (38.9%) patients needed an orchiectomy. After analysis, TT and consequent orchiectomy were associated with a longer interval between SP onset and PED arrival, absent of testicular ultrasonic blood flow, interval between SP onset and surgery of more than 24 hours, and a high degree of TT. None of them experienced recurrent SP symptoms or TT again., Conclusions: The rate of TT in patients presenting to PEDs with an SP was 28.1%, and 38.9% of the patients with TT needed an orchiectomy. Early diagnosis and intervention helped to prevent subsequent orchiectomy in pediatric patients with TT., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Testicular 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., Objectives: To 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 Methods: We reviewed all original research and epidemiological papers related to testicular torsion condition., Results: Testicular 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 Conclusion: To 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., (© 2023 American Society of Andrology and European Academy of Andrology.)

Testicular torsion is considered a urological disorder that requires immediate detorsion surgery. Ischemia/reperfusion (I/R) injury after testicular torsion detorsion causes of drastic impairment of spermatogenesis and infertility. Cell-free-based approaches seem to be a promising strategy to prevent I/R injury, they have more stable biological properties, and they contain paracrine factors of mesenchymal stem cells. The purpose of this study was to evaluate the protective effects of human amniotic membrane derived mesenchymal stem cells (hAMSCs) secreted factors on mouse sperm chromatin condensation and spermatogenesis improvement after I/R injury. hAMSCs were isolated and characterized by RT- PCR and flow cytometry, preparation of hAMSCs secreted factors was performed. Forty male mice were randomly divided into 4 groups: sham-operated, torsion detorsion, torsion detorsion+ intratesticular injection of DMEM/F-12, and torsion detorsion+ intratesticular injection of hAMSCs secreted factors. After one cycle of spermatogenesis, the mean number of germ cells, Sertoli, Leydig, myoid as well as tubular parameters, Johnson score, and spermatogenesis indexes were evaluated by H& E and PAS stainings. Sperm chromatin condensation and relative expression of c-kit and prm 1 genes were assessed by aniline blue staining and real-time PCR, respectively. The mean number of spermatogenic cells, Leydig, myoid, Sertoli, spermatogenesis parameters, Johnson score, as well as germinal epithelial height and diameters of seminiferous tubules decreased significantly after I/R injury. The thickness of basement membrane and percentage of sperm with excessive histone significantly increased, while the relative expression of c-kit and prm 1 significantly decreased in torsion detorsion group (p 0.001). hAMSCs secreted factors remarkably restored normal sperm chromatin condensation, spermatogenesis parameters and histomorphometric organization of seminiferous tubules via intratesticular injection (p 0.001). Thus, hAMSCs secreted factors may potentially salvage torsion-detorsion-induced infertility., Competing Interests: Conflict of Interests The authors declare no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Torsion of the spermatic cord is a urological emergency that must be treated immediately with surgery, yet detorsion of the testis can cause testicular tissue damage because of ischemia-reperfusion (I/R) injury. I/R injury is a complex pathophysiological process that may affect the functions of distant organs. Here, we examined whether testicular torsion/detorsion (TT) causes myocardial dysfunction. We next investigated the potential beneficial effect and underlying mechanisms of remote ischemic postconditioning (RIPost) on cardiac function after testicular torsion/detorsion. Male Sprague-Dawley rats were assigned to three different sets of experimental groups. Testicular I/R was induced by rotating the right testis to 1080° clockwise for 3 h followed by 3 h of detorsion. RIPost was induced at the onset of testicular detorsion by four cycles of 5-min bilateral femoral artery occlusion with 5-min reperfusion. Cardiac function was determined postdetorsion, and the cardioprotective effect of RIPost was examined. Testicular torsion/detorsion-treated rats had reduced serum testosterone levels, impaired systemic hemodynamics, elevated systemic inflammatory responses, and increased serum levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), α-hydroxybutyrate dehydrogenase (α-HBDH), and cardiac troponin I (cTnI). However, RIPost attenuated remote heart dysfunction induced by testicular torsion/detorsion. Furthermore, RIPost enhanced the phosphorylation of ventricular signal transducer and activator of transcription (STAT)-3, which is a key component of the survivor activating factor enhancement (SAFE) signaling pathways. Inhibition of STAT-3 with Ag490 abolished the RIPost-induced cardioprotection and STAT-3 phosphorylation. Testicular torsion followed by detorsion may cause impaired cardiac function in rats. RIPost effectively attenuates this remote cardiac dysfunction. RIPost-induced protective effects may be mediated by the STAT-3 signaling pathway.

Rationale: Rare side effects of acute epididymitis include testicular infarction and ischemia. Distinguishing them from testicular torsion is challenging, both clinically and radiologically. However, only a few such cases have been reported to date., Patient Concerns: A 12-year-old child presented with persistent right testicular pain for 3 days. It developed after trauma and was accompanied by gradual swelling and enlargement of the right scrotum, with nausea and vomiting. Scrotal color Doppler ultrasonography demonstrated right epididymitis, right scrotal wall swelling, and right testicular torsion. Routine blood tests revealed leukocyte and neutrophil counts were both above normal., Diagnosis: Scrotal exploration revealed edema and adhesions in all layers of the scrotal wall. The right testicle was pale. The patient was diagnosed with testicular ischemia secondary to acute epididymitis., Interventions: The patient underwent simultaneous lower spermatic cord sheath dissection and decompression, testicular sheath reversal, and right testicular fixation., Outcomes: Blood flow to the testicles gradually recovered after decompression, as did the color. Postoperatively, the patient's scrotal swelling and pain improved significantly., Lessons: Despite the rarity of this condition, it is a potentially serious consequence of epididymitis and should be considered when patients experience sudden scrotal pain., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Study Question: Is prior testicular torsion associated with testicular function (semen quality and reproductive hormones) in young men from the general population?, Summary Answer: In young men from the general population, no differences in semen parameters were observed in those who had experienced testicular torsion compared to controls and observations of higher FSH and lower inhibin B were subtle., What Is Known Already: Testicular function may be impaired after testicular torsion, but knowledge is sparse and based on studies with small sample sizes and no control group or a less than ideal control group., Study Design, Size, Duration: A cross-sectional population-based study was carried out including 7876 young Danish men with unknown fertility potential, examined from 1996 to 2020., Participants/materials, Setting, Methods: All men (median age 19.0 years) had a physical examination, provided a blood and semen sample, and filled in a questionnaire including information about prior testicular torsion, birth, lifestyle and current and previous diseases. Markers of testicular function, including testis volume, semen parameters and reproductive hormones, were compared between men operated for testicular torsion and controls, using multiple linear regression analyses., Main Results and the Role of Chance: The average participation rate was 24% for the entire study period. In total, 57 men (0.72%) were previously operated for testicular torsion (median age at surgery 13.4 years) of which five had only one remaining testicle. Men with prior testicular torsion were more often born preterm (25% versus 9.5% among controls), and they had significantly higher FSH and lower inhibin B levels, and a lower inhibin B/FSH ratio than controls in crude and adjusted models. The association was mainly driven by the subgroup of men who had undergone unilateral orchiectomy. No differences in semen parameters were observed., Limitations, Reasons for Caution: A limitation is the retrospective self-reported information on testicular torsion. Also, results should be interpreted with caution owing to the high uncertainty of the observed differences., Wider Implications of the Findings: Overall, the results of our study are reassuring for men who have experienced testicular torsion, especially when treated with orchiopexy, for whom reproductive hormone alterations were subtle and without obvious clinical relevance. Our study found no differences in semen parameters, but follow-up studies are needed to assess any long-term consequences for fertility., Study Funding/competing Interest(s): Financial support was received from the Danish Ministry of Health; the Danish Environmental Protection Agency; the Research fund of Rigshospitalet, Copenhagen University Hospital; the European Union (Contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603, FP7/2007-2013, DEER Grant agreement no. 212844); A.P. Møller and wife Chastine Mckinney Møllers Foundation; Svend Andersens Foundation; the Research Fund of the Capital Region of Denmark; and ReproUnion (EU/Interreg). The authors have nothing to declare., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This investigation aimed to evaluate the defensive impacts of citral on ischemia/reperfusion (I/R) injury induced by testicular torsion/detorsion (T/D) in rats in an experimental model. The grouping of subjects was as follows: (1) sham, (2) T/D, (3) and (4) T/D plus citral 150 and 300 mg/kg, respectively, and (5) intact (citral 300 mg/kg). T/D was performed by testicular 720° turning for 2 h and then detorsion for 24 h. Blood serum was obtained to assess testosterone and oxidative stress markers, epididymal sperms were collected for sperm staining and sperm analysis, and testicular tissues were examined for histopathology. T/D damage was associated with a remarkable decline in sperm total count, viability, and some velocity parameters in comparison to the sham group (p < 0.05), which could be reversed significantly by citral (p < 0.05). Histopathologically, T/D damage caused severe oedema, haemorrhage, inflammation, and seminiferous tubules disruption, while citral improved significantly the mean seminiferous tubular diameter, Cosentino's score, and Johnsen's score (p < 0.05). I/R injury was associated with significant increased malondialdehyde and oxidative stress index, and also significant reduced total antioxidant capacity and testosterone versus the sham group (p < 0.05), which all were prevented significantly by citral administration (p < 0.05). The outcomes greatly proved that testicular I/R injury could be significantly prevented by citral., (© 2022 Wiley-VCH GmbH.)

Testicular ischemia-reperfusion injury (TIR) is a urological emergency common among male newborns, children, and adolescents. Testicular injury and its consequences, such as altered hormone production, subfertility, and infertility, are determined by the duration and degree of testicular torsion. Early diagnosis and treatment are crucial to preserving the testes and fertility. Previous studies suggest that reactive oxygen species contribute to the pathogenesis of TIR injury, but the underlying mechanism remains unclear. Several drugs/plants reportedly exhibit antioxidative activities to protect against TIR. This review summarizes current studies on the role of antioxidants in preventing experimental TIR injury and discusses the underlying pathophysiological mechanisms.

Introduction: The TWIST score is a 5-component physical examination score used to aid in diagnosis of testicular torsion (TT) and could lessen need for radiologic testing in certain clinical scenarios., Objective: TWIST use was not previously widespread at our institution. The primary objective of this quality improvement study was to achieve 100% compliance in TWIST utilization among urology and ED residents and to assess for score concordance between ED and urology assessments. Secondary goals were correlation of TWIST components with need for orchiectomy., Methods: ED staff were educated about the TWIST score and asked to complete assessment for patients presenting with acute scrotal pain. Simultaneously, an electronic medical record-based dot phrase was introduced for urology trainees to complete an independent TWIST evaluation. Spearman correlation was performed to assess association between ED and Urology TWIST scores. Multivariable logistic regression was performed to assess association of TWIST score components and need for orchiectomy., Results: 103 patients presented to the ED from 3/2018-11/2020 with a complaint of acute scrotal pain; 47 were diagnosed with torsion. As compared to our retrospective cohort, the documentation rate of complete TWIST score components on exam rose from 9% to 98% (P < 0.001) on ED evaluation and 16%-66% on urology evaluation (P < 0.001). Rates of repeat ultrasound for patient's transferred between facilities was similar (58% vs. 63%; p = 0.66) as was median time to OR (160 min vs. 145 min; p = 0.5). Using TWIST cutoff of >5 yielded a specificity of 94.5% for diagnosis of torsion, with corresponding strong correlation between ED and urology scores (rho = 0.71). A firm testicle was noted on urology evaluation in 100% of orchiectomy patients (vs. 61% of salvage patients) with persistent association after controlling for duration of symptoms (OR 28.1; P = 0.016)., Discussion: Through two-pronged quality improvement efforts, we significantly improved utilization of the TWIST score by ED and urology staff for workup of patients with acute testicular pain. We confirmed the high sensitivity and specificity of the TWIST score and demonstrated inter-rater reliability between ED and urology assessments. On prospective analysis, testicular firmness on exam was predictive of need for orchiectomy., Conclusion: The TWIST score is an accurate diagnostic tool for both ED and urology providers in workup of children with acute scrotal pain, with a normal score essentially ruling out the condition. Future work should aim at minimizing unnecessary testing in patients demonstrated to be at high risk for torsion., Competing Interests: Declarations of Interest None., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Testicular torsion (TT) is an acute inflammatory process leading to male infertility. Today, anti-inflammatory effects of exosomes derived from blood serum are used in various laboratory procedures. In the present study, the anti-inflammatory effects of blood-serum-derived exosomes in treatment of acute inflammation following TT in mice were evaluated., Materials and Methods: Eighteen male mice were grouped as healthy control, TT, and TT + exosome. TT was induced surgically, and exosomes were extracted from blood serum and administrated by a single intratesticular injection (10 IU). Malondialdehyde (MDA) and Griess assays were used to evaluate the level of oxidative stress. Sperm indices, testosterone (Tes), and apoptotic gene expression (p-53, Bcl2, and Caspase-3) were also assessed. H&E and immunohistochemistry (IHC) stainings were used for histopathological investigations. Data analysis was applied by SPSS (v.19) software., Results: Oxidative stress and apoptotic genes expression were increased significantly (p < 0.05) in TT group compared with control. Sperm parameters and Tes were significantly increased, and expression of apoptotic genes was significantly reduced in TT + exosome group (p < 0.05)., Conclusion: Since the blood-serum-derived exosomes have anti-inflammatory features, the intratesticular application of blood-serum-derived exosomes can be used clinically in acute phase of orchitis following TT to inhibit testicular inflammation., (© 2022 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Testicular torsion/detorsion-induced ischemia/reperfusion injury is partly due to the overgeneration of reactive oxygen species. Baicalein, a main bioactive constituent derived from the dried root of Scutellaria baicalensis Georgi, possesses powerful antioxidative and anti-inflammatory properties. Therefore, we designed the research to explore the possible protective effect of baicalein against testicular ischemia-reperfusion injury. Sprague-Dawley rats were randomized into 4 groups, including control, testicular ischemia-reperfusion, testicular ischemia-reperfusion+vehicle injection, and testicular ischemia-reperfusion+baicalein therapy groups. The control group received surgical exposure of the left testis without torsion-detorsion. In the testicular ischemia-reperfusion group, the left testis underwent 720° counterclockwise torsion for two hours and then was allowed detorsion. Rats in the testicular ischemia-reperfusion+vehicle injection group received intraperitoneal injection of the vehicle at detorsion. In the baicalein-treated group, the intraperitoneal administration of baicalein dissolved in the vehicle was performed at detorsion. At four hours or three months following testicular detorsion, testicular tissues were removed to detect the levels of tumor necrosis factor-alpha (TNF- α ) and interleukin-1beta (IL-1 β ) which can recruit neutrophils into the testis, myeloperoxidase activity (an index of neutrophil infiltration in the testis), protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in neutrophils which can catalyze reactive oxygen species production, malondialdehyde concentration (a common marker of reactive oxygen species), and spermatogenesis. Both testicular ischemia-reperfusion and testicular ischemia-reperfusion+vehicle injection significantly increased the TNF- α and IL-1 β levels, myeloperoxidase activity, NADPH oxidase protein expression, and malondialdehyde concentration, while decreased spermatogenesis in ipsilateral testes. In contrast, baicalein administration remarkably reduced TNF- α and IL-1 β levels, myeloperoxidase activity, NADPH oxidase protein expression, and malondialdehyde concentration and also elevated spermatogenesis in ipsilateral testes. The results of our experiment demonstrate that baicalein alleviates testicular ischemia-reperfusion injury by inhibiting TNF- α and IL-1 β secretion, neutrophil infiltration in the testis, and NADPH oxidase protein expression in neutrophils to reduce reactive oxygen species production., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this article., (Copyright © 2022 Si-Ming Wei and Yu-Min Huang.)

Objective: To determine if empirical antibiotic treatment for non-testicular torsion (NNT) acute scrotum is necessary in the setting of a normal urine analysis (UA)., Methods: Retrospective chart review revealed 314 pediatric patients with clinically diagnosed NTT acute scrotum with negative UA between 2004-2019. Exclusion criteria included previous urological history and immunocompromised state. Patients were divided into those with antibiotics treatment vs those without. The independent t test was used to compare numerical variables while the chi-squared test was used to compare categorical variables., Results: Of the 314 patients identified, 141 (44.9%) received empiric antibiotics despite negative UA. Clinical findings and demographic characteristics between groups were not found to be significant. Patients clinically diagnosed with epididymo-orchitis were more likely to be prescribed antibiotics (48.2 vs 30.6%, P =.02). Trimethoprim-sulfamethoxazole accounted for 83% of the antibiotics that were prescribed in our study. There was no significant difference in symptom resolution between patients prescribed antibiotics and those not prescribed antibiotics (5.1 days vs 4.6 days, P =.71). Additionally, no patient in either group returned with complications such as worsening symptoms or urinary tract infection between presentation and their scheduled follow up visit., Conclusion: Based on our analysis, antibiotics in NTT acute scrotum appear to have no benefit in symptom resolution or complication reduction in patients without any predisposing urological risk factors and negative UA at presentation. Given the risk and rise of antibiotic resistance providers need to be careful to select treatments based on available evidence., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In this research, the effects of betaine on testicular ischemia-reperfusion were evaluated. Forty rats were randomly divided into 4 groups of sham, torsion/detorsion (TD), torsion/detorsion with two different dosage of betaine 200 mg/kg, and 300 mg/kg, respectively. At the end of the experiment, the testosterone concentration, sperm motility, concentration and vitality, oxidative stress biomarkers including Malondialdehyde (MDA), Glutathione peroxidase (GPx), Catalase (CAT), and total antioxidant capacity (TAC) were assessed. Moreover, histopathological parameters including seminiferous tubules diameter (STD), seminiferous epithelium thickness (SET), spermatogonia nuclei diameter (SpND), Sertoli cell nuclei diameter (StND) and miotic index were evaluated. The testosterone concentration altered during torsion/detorsion and betaine could increase slightly the testosterone concentration after 15 days. Sperm motility and vitality significantly increased in the betaine treated groups compared to the TD group on days 3 and 15. Among oxidative stress biomarkers, only CAT on day 3 and GPx on day 15 were significantly higher in the betaine groups compared to the TD group. Among histopathological parameters an increase in the STD and SET in betaine-200 and betaine-300 groups were observed on 15th day of post-surgery, compared to the TD group. These findings indicate that betaine can ameliorate testicular damages triggered by torsion/detorsion., (© 2022 Wiley-VCH GmbH.)

Acute scrotal pain (ASP) requiring surgical exploration is common in the pediatric population, but little has been reported on this subject with regard to the adult population. The aim of this study was to investigate the demographic and clinical characteristics and outcomes of scrotal explorations performed on adult patients. Patients over 21 years of age who underwent surgical exploration for ASP with suspected testicular torsion (TT) at 14 French hospitals between January 2005 and December 2019 were included in this study. The main outcome measures were demographic characteristics, pathology found during scrotal exploration, and perioperative outcomes. Logistic regression was used to perform univariate and multivariate analyses to identify predictors of TT. Data for 1329 men were analyzed. The median age was 30 (interquartile range [IQR]: 25-35; range: 21-89) years. Regarding the clinical examination, 867 (65.2%) patients presented with an elevation of the testicle, 613 (46.1%) patients with scrotal edema or erythema, and 211 (15.9%) patients with nausea or vomiting. Operative findings identified TT in only 684 (51.5%) patients, epididymo-orchitis in 112 (8.4%) patients, a tumor in 16 (1.2%) patients, and no causes in 475 (35.7%) patients. Orchiectomy for nonviable testes was required in 101 (7.6%) patients. In multivariate analysis, an elevation of the testicle, erythema/swelling, and the presence of nausea/vomiting were found to be associated with the occurrence of TT. Testicular torsion is not exclusive to children and adolescents, so must be considered in males of any age with acute scrotal findings. However, one-third of scrotal explorations in adults did not lead to a diagnosis., Competing Interests: None

Background: The estimated incidence of testicular torsion (TT) is 4 per 100,000 males under 25 years [1]. Age, region and health insurance status have been associated with a higher risk of orchidectomy following TT [2]., Aims: This study aimed to establish incidence rates for TT in Ireland for the first time. Sociodemographic characteristics were analysed to assess risk factors for undergoing orchidectomy., Methods: A retrospective analysis of a national database, Hospital In-Patient Enquiry (HIPE), was carried out. Cases of TT treated between 2009 and 2018 were identified. Incidence and age-specific rates were calculated in conjunction with census data. Descriptive statistics, non-parametric tests and logistic regression were used to evaluate risk factors for orchidectomy., Results: Between 2009 and 2018, 1746 males under 25 years underwent scrotal exploration for TT. The crude incidence was 21.76 per 100,000 population. The age-standardised rate rose from 16.85 per 100,000 in 2009 to 26.31 per 100,000 in 2018. TT was most common in the 10-14 years age-group (n = 766, 43%) with a normal distribution across age-groups. TT most commonly occurred in spring (27.55%, 95% CI 25.46-29.71%), and was least common in summer (21.65%, 95% CI 19.46-23.36%, p < 0.01). Age, lack of private insurance, province of residence and transfer from another hospital were associated with orchidectomy., Conclusions: The incidence of TT appears to be higher in Ireland than elsewhere. Epidemiological data for TT in Ireland will help inform health policy and clinical guidelines, facilitate comparison with other jurisdictions and improve public awareness. Further research is needed to identify modifiable risk factors that predict treatment outcomes., (© 2021. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Background: Ischemia-reperfusion injury (IRI) is the key reason of injury after testicular torsion and may eventually lead to male infertility. Oleuropein, a natural antioxidant isolated from Olea europaea, has shown beneficial effects in different models of ischemia. We evaluated the effects of oleuropein on testicular IRI and explored the underlying protective mechanisms., Methods: A mouse testicular torsion/detorsion (T/D) model and an oxygen-glucose deprivation/reperfusion (OGD/R) germ cell model were established and treated with oleuropein. H&E staining was used to evaluate testicular pathological changes. Apoptosis and apoptosis-associated protein levels in testis tissues were assessed by TUNEL staining, immunohistochemical staining and western blot. Apoptosis levels and apoptosis-associated protein levels in GC-1 were evaluated by flow cytometry, immunofluorescence and western blot. Oxidative stress levels were assessed by malondialdehyde (MDA) and superoxide dismutase (SOD) kits. Cell viability and inflammatory protein levels were evaluated by CCK-8 assay coupled with qRT-PCR., Results: Relative to the control group, SOD activity was markedly suppressed, while MDA, Bax, Caspase-3, TNF-α as well as IL-1β levels were significantly increased in the T/D model and OGD/R model. However, all of the aforementioned alterations were relieved by oleuropein treatment., Conclusion: Our findings indicate that oleuropein may be a promising treatment option to attenuate testicular IRI via its anti-oxidant, anti-inflammatory as well as anti-apoptotic properties., Competing Interests: Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: This study aimed to biochemically and histopathologically investigate the effect of sunitinib on oxidative testicular damage induced by ischemia/reperfusion in rats., Material-Method: Experimental animals were divided into three groups of six rats each: testicular torsion-detorsion (TTD), sunitinib+testicular torsion-detorsion (STD), and sham control (SC). Sunitinib (25mg/kg) was administered orally to the STD group by gavage. Normal saline (0.9% NaCl) was administered orally to the TTD and control groups as the solvent. One hour after administration of sunitinib and 0.9% NaCl, all animal groups were done torsion-detorsion. Then, all the rats were killed by high-dose anesthesia, and their testicles were removed. Biochemical and histopathological examinations were performed on the removed testicular tissues., Results: Malondialdehyde; it was observed that the results in the STD group were close to those of the SC group and statistically significant lower compared to the TTD group (p=0.001). The glutathione values were statistically significantly higher in the STD group compared to the TTD group (p<0.001). Nuclear factor kappa B values, revealing a statistically significant difference between the TTD and STD groups (p<0.001). The TNF-α levels were measured and indicating that the results of the STD group were statistically significantly lower than those of the TTD group (p<0.001). Histopathologically, animal tissues given sunitinib were observed to resemble normal tissues., Conclusion: Sunitinib was shown to prevent histopathological changes in testicular tissue against ischemia/reperfusion damage., (Copyright © 2021 Asociación Española de Andrología, Medicina Sexual y Reproductiva. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: To evaluate the impact of insulin like growth factor-1(IGF-1) and growth hormone (GH) on testis histology, spermatogenesis, and fertility in prepubertal rats exposed to 6 h of testicular torsion (TT) and detorsion., Material-Method: Forty-eight male Wistar-albino rats weighing 30-70g and at 3-week age were allocated into six groups involving eight rats in each group as follows: Group 1:Sham, Group 2:Control, Group 3:Gelatin, Group 4:Local-IGF-1, 5: Local-GH, Group 6: Systemic-GH. Right testis was only exposed and sutured in the sham group, and right testes were rotated clockwise, 720°, fixed, and 6 h later, detorsion on the testis was done in groups 2-6. Unloaded gelatin, 5 μg local-IGF-1 loaded, and 2IU rhGH loaded gelatin were sutured to the right testis after detorsion in groups 3-5. In Group 6, 0.3IU/100gr/d rhGH was given for seven days via subcuticular route after detorsion. Each of the rats cohabited with two female rats five weeks later. Afterward, both right and left testes were removed. Mean diameter of seminiferous tubules (STD), mean biopsy score count of the testis (TBSC), mean percentage of haploid cells (HCP) were assessed, and fertility parameters were evaluated., Results: STD and TBSC of the ipsilateral testes were significantly reduced in control and gelatin groups when compared to sham, local-IGF-1, and local-GH groups. STD and TBSC of the ipsilateral testes of the systemic-GH group were decreased compared to the sham group. HCP of the ipsilateral testes of control, gelatin, and systemic-GH groups were significantly lower than the sham, local-IGF-1, and local-GH groups. STD, TBSC, and HCP of the contralateral testes were significantly reduced in control and gelatin groups when compared separately to sham, local-IGF-1, systemic- GH, and local-GH groups. The difference between groups regarding potency, fertility, fecundity indexes, and mean fetus numbers were not significant., Conclusion: Even though there was significant and permanent histologic germ cell damage and reduced HCP in both ipsilateral and contralateral testes, experimental 6 h TT and detorsion in prepubertal rats did not have a negative impact on future fertility. Local-IGF-1and rhGH treatment improved germ cell histology and spermatogenesis in both ipsilateral and contralateral testes of prepubertal rats, subjected to 6 h of TT and detorsion., Competing Interests: Conflicts of interest None., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Testicular torsion/detorsion can lead to severe testicular damage. The organ-protective effect of remote ischemic postconditioning (RLIPost) against ischemia/reperfusion injury has been characterized; however, it remains unknown whether RLIPost has a testicular protective effect., Objectives: Here, we tested the hypothesis that RLIPost can protect the testes in a rat model of testicular torsion/detorsion in vivo., Materials and Methods: Male Sprague-Dawley rats were assigned to sham-operated, control, or remote liver and limb ischemic postconditioning-treated groups. Testicular torsion/detorsion was performed by 3 h of testicular torsion (720° clockwise unilateral spermatic cord torsion), followed by 3 h of detorsion. For liver and limb ischemic postconditioning, four cycles of 5 min of liver or limb ischemia with 5-min intermittent reperfusion stimuli were conducted at the onset of testicular reperfusion., Results: Liver and limb ischemic postconditioning significantly ameliorated ipsilateral and contralateral testicular swelling responses, preserved morphological integrity and spermatogenesis and inhibited testicular apoptosis. In addition, RLIPost enhanced the phosphorylation of AKT/ERK1/2/GSK-3β/STAT-3 in the ipsilateral testis while suppressing JNK activation in the ipsilateral and contralateral testes., Discussion and Conclusion: To the best of our knowledge, this study is the first to demonstrate the involvement of RLIPost in an animal model of testicular torsion/detorsion. We showed that RLIPost protects both ipsilateral and contralateral testes against testicular torsion/detorsion in vivo, via at least in part, the RISK and SAFE-mediated signaling pathways., (© 2022 American Society of Andrology and European Academy of Andrology.)

Background: One of the types of catabolic processes in cells is autophagy, which maintains cell homeostasis. It is also known as a defense response to oxidative stress. This study aimed to track the autophagic activity of testicular tissue in mature and immature rats in 3 conditions: (1) physiologic, (2) under increased pressure in the tunica albuginea compartment following the induction of testicular torsion, and (3) decompression of this compartment by flap technique., Methods: This study was performed on 72 Wistar rats divided into 3 mature and 3 immature groups, each of the groups including Sham group, testicular torsion induction group for 6 hours (Torsion Detorsion), and testicular torsion induction group for 6 hours, followed by the flap technique., Results: In the physiologic state or Sham, autophagic indices (LC3, Beclin-1) are active, and more activity was observed in mature rats, compared with immature ones, which indicated the activity of this process during development and maturity. In the Torsion Detorsion group, significant expression of autophagy and apoptosis indices (caspase3) was observed along with the degradation of spermatogenesis and steroidogenesis. It seems that in this state, the activation of autophagy leads to programmed death and is in line with apoptosis. Finally, in the flap technique group, an increase in the expression of autophagy indices was accompanied by a reduction in the expression of apoptotic indices and improved spermatogenesis and steroidogenesis., Conclusion: Decompression of tunica albuginea by flap technique can activate of autophagy process to save tissue function and eliminate stress caused by testicular torsion., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We describe and summarize the diagnosis, treatment, and reasons for delayed treatment of children with cryptorchidism torsion in Children's Hospital of Chongqing Medical University. The study included 19 cases of cryptorchidism torsion. The age of the children ranged from 16 days to 12 years (median: 6 years). The interval from diagnosis to surgery varied from 4 h to 16 days (median: 3 days). Ultrasound was performed in all cases. Fifteen cases had cryptorchidism torsion, 2 cases had a soft tissue mass in the inguinal region, and 2 cases had an inguinal/abdominal teratoma. Five cases were treated with an orchidopexy, 12 cases were treated with orchiectomy, and 2 cases received resection of a testicular tumor. The 5 children with an orchidopexy were followed up from 1 month to 7 years (median: 3 years), with 1 child having a testis retraction and no blood supply. Of the 12 children who had an orchiectomy, three had delayed diagnosis due to family unawareness of the condition, while other delays were due to delayed referral from primary care facilities. The relative rarity and insufficient awareness of cryptorchidism torsion resulted in a low rate of testicular salvage. Therefore, hospitals of all levels should be fully aware of cryptorchidism with torsion and ensure a male child's genital system and inguinal region are examined to improve the success rate of testicular salvage., Competing Interests: None

Backround: Testicular torsion (TT) is an urological emergency situation especially in adolescents and young men. The main pathophysiology of testicular torsion/detorsion (T/D) is ischemia-reperfusion (I/R) injury. I/R induces the production of reactive oxygen species (ROS) thought to play a critical role in tissue injury. Increasing evidence suggests that ER stress may play an important role in I/R-induced cell death. During ischemia, oxygen and glucose deprivation also causes abnormalities in protein folding processes. Antioxidants suppress oxidative stress directly as well as ER stress and thus gain importance in the treatment of pathologies associated with oxidative stress and ER stress, such as I/R damage. Chlorogenic acid (CGA) which is formed by the esterification of caffeic and quinic acids and is one of the most abundant phenolic acids in nature. There is also a growing body of studies reporting protective effects of CGA against I/R injury in different tissues, including intestinal, heart and brain., Objective: To investigate the effects of CGA on oxidative stress and ER stress in an experimental testicular I/R injury model., Design: Rats were divided into three groups: control, T/D, and T/D + CGA. In the T/D + CGA group, 100 mg/kg CGA was given intraperitoneally 30 min before detorsion. While tissue malondialdehyde (MDA) levels were determined manually using a colorimetric method, tissue superoxide dismutase (SOD), 78-kDa glucose regulatory protein (GRP78), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP) levels were determined enzyme-linked immunosorbent assay (ELISA) kits. Johnsen's testicle scoring system was used for histological evaluation., Results: In T/D group, tissue MDA, GRP78, ATF6 and CHOP levels were significantly higher than control group (p < 0.05). These increases were significantly reversed with CGA pre-treatment (p < 0.05). The histopathological Johnsen score was significantly lower in the T/D group compared to the control group, but the level of histopathological Johnsen score was significantly restored by CGA pre-treatment (p < 0.05)., Discussion: The relationship between I/R injury and ER stress has been emphasized frequently in recent years. This study in which the effects of CGA on TT were examined for the first time, showed that CGA can inhibit I/R-induced testicular damage., Conclusion: These results may provide a new insight into CGA and may form the first clinical theoretical basis for the possible use of CGA in the treatment of TT in the future. However, the real function of CGA in TT patients needs further investigation., Competing Interests: Conflicts of interest There are no conflicts of interest., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Aim: Testicular ischaemia/reperfusion (I/R) injury is a major consequence of testicular torsion with possible attendant risk of male infertility. Glutamine, on the other hand, is a known antioxidant with anti-inflammatory potential. The present study evaluated whether or not glutamine would improve I/R-induced testicular injury in torsion/detorsion (T/D). The possible associated mechanisms were also investigated., Methods: Wistar rats were randomly allotted into four groups (n = 10); sham-operated, glutamine-treated, T/D, and T/D + glutamine. Testicular torsion was induced and reperfusion established after two and a half hour under ketamine/xylazine anaethesia. Glutamine was administered one hour before reperfusion and continued daily for 3 days. At the end of the study, animals were euthanized, blood samples obtained, epididymal sperm suspension collected, and the testes harvested for biochemical and histopathological assays using established methods., Results: Glutamine prevented T/D-driven I/R-induced reduced sperm quality, impaired testicular histoarchitecture, and suppressed circulating testosterone. Also, glutamine abated I/R-induced oxidative stress (evidenced by reduced hydrogen peroxide and MDA generation and enhanced concentrations and activities of antioxidants), inflammation (evidenced by suppression of TNF-α and IL-1β), and apoptosis (evidenced by reduced DNA fragmentation) by down-regulating NF-kB and caspase 3 activity., Conclusion: For the first time, this study demonstrated that glutamine administration improved testicular I/R injury in T/D rat model by maintaining testicular redox balance, and testicular integrity and function via inhibition of I/R-induced upregulation of NF-kB signaling and caspase 3 activation., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Testicular torsion-detorsion is an ischaemia-reperfusion-induced male gonad injury that may lead to male infertility. Oxidative stress plays an important role in the ischaemia-reperfusion injury. Icariside II (ICA II) prevents oxidative stress and has obvious protective effects on spermatogenic function. The present study was aimed to investigate therapeutic potentials of ICA II on testicular torsion. 72 mice were randomly divided into three groups: sham-operated control group (n = 24), testicular ischemia-reperfusion + saline group (n = 24) and testicular ischemia-reperfusion + icariside II treated group (n = 24). Testicular ischemia-reperfusion was induced by the left testis rotated 360 degrees in a clockwise direction for 30 minutes followed by detorsion, the contralateral testis was removed. ICA II in saline (5 mg/kg/day) was administrated by gavage immediately after detorsion. The results demonstrated that ICA II alleviated testicular damage by mitigating spermatogenic cell injury and improving testosterone production in mouse models of testicular torsion. We revealed that ICA II alleviated oxidative stress and apoptosis in the testes, reduced inflammatory infiltration and accelerated angiogenesis. Briefly, ICA II administration ameliorated testicular damage by improving spermatogenic function and testosterone production, which supports its use as a pharmacological treatment of testicular torsion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chi, Yang, Cao, Wang, Liu, Dai, Deng and Zhang.)

Background: The aim of this study was to investigate the effects of astaxanthin (ASX) on testicular torsion/detorsion (T/D) damage in rats in terms of oxidative stress and endoplasmic reticulum (ER) stress., Methods: Eighteen male Sprague-Dawley rats were divided into three groups with six rats in each group: control, T/D and T/D + 20 mg/kg ASX. Torsion and detorsion times were applied as 4 h and 2 h, respectively. ASX application was performed 30 minutes before detorsion. At the end of the period, testicular tissues were removed and biochemical and histological analyzes were performed. To evaluate the degree of oxidative stress, tissue malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) were determined using colorimetric methods, while tissue superoxide dismutase (SOD) levels were determined using ELISA kit. To evaluate the degree of ER stress, tissue glucose regulatory protein 78 (GRP78), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP) levels were determined using ELISA kits. Johnsen's testicle scoring system was used for histological evaluation., Results: In the T/D group, it is determined that statistically significant decreasing in TAS, SOD levels and Johnsen score, and increasing in TOS, OSI, MDA, GRP78, ATF6 and CHOP levels (p < 0.001) compared with control group. ASX administration statistically significantly restored this T/D-induced damage (p < 0.01)., Conclusion: This is the first study to show that ASX prevent T/D-induced testicular damage through its antioxidant activity. More comprehensive studies are needed to see the underlying mechanisms.

Background: The purpose of this study was to evaluate the possible therapeutic effect of chrysin (CHS) on testicular torsion/detorsion (T/D) injury in vivo through the mechanisms of oxidative stress and endoplasmic reticulum stress (ERS)., Methods: Eighteen male rats were divided into three groups of six subjects in each group: control, T/D and T/D + CHS (100 mg/kg). To evaluate the degree of oxidative stress, tissue malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) levels were determined using colorimetric methods, while tissue superoxide dismutase (SOD) levels were determined using an ELISA kit. To evaluate the degree of ERS, tissue glucose regulatory protein 78 (GRP78), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP) levels were determined using ELISA kits. Johnsen's testicle scoring system was used for histological evaluation., Results: In the T/D group, it is determined that statistically significant decreasing in the levels of TAS, SOD and Johnsen score, and increasing in TOS, MDA, GRP78, ATF6 and CHOP levels compared to control group (p < 0.05). CHS administration statistically significantly restored this T/D-induced damage (p < 0.05)., Conclusion: This is the first study to show that CHS prevent T/D-induced testicular damage through its ERS inhibitor activity. More comprehensive studies are needed to understand the underlying mechanisms., Supplemental data for this article is available online at https://doi.org/10.1080/08941939.2021.2015489 .

Background: Testicular torsion is still an urgent surgical condition and without any treatment it can cause infertility. The main pathophysiology of testicular torsion ischaemic injury however; the main sequalae of detorsion is reperfusion injury. Furthermore; treatments to prevent ischemic reperfusion injury due to decreased blood flow are important to preserve testicular function., Aims: Human chorionic gonadotropin β (β-hCG) is an anabolic hormone that supports steroidogenesis and spermatogenesis. Vitamin C (Vit-C) is one of the water-soluble vitamins and is also a potent antioxidant in ischemic damage. Moreover, it has protective effects by increasing blood and lymph flow in the testicles. The aim of this study is to investigate the effects of β-hCG, Vit-C and their combination on ischemic reperfusion injury occurring after surgical treatment of testicular torsion., Study Design: Animal research studies., Methods: The study was performed on 25 male Wistar albino rats. The animals were divided equally into 5 groups. In the first group "Control Group," left orchiectomy was performed. In the second group "Sham Group," a 720° clockwise torsion was created and after 4 h of left testicular torsion it was detorsioned for 4 h and then left orchiectomy was performed. In the third group same procedure was applied with 30 mg vitamin C was administered via intraperitoneal route once a week for 3 weeks. In the fourth group after same surgical procedures 75 IU β-hCG was administered via intraperitoneal route once a week for 3 weeks. In the fifth group after 4 h left testicle torsion it was detorsioned for 4 h then, 75 IU β-hCG and vitamin C together were administered via intraperitoneal route once a week for 3 weeks. Left orchiectomy was performed after 3 weeks in the third, fourth and fifth groups. Specimens were evaluated histologically., Results: Testicular tissue histopathological evaluations were performed. A high histopathological stage indicates more testicular damage, and a low one was indicated less testicular damage. The average histopathological grade of vitamin C + β-hCG group was significantly higher than the average histopathological grade of the control, the sham group and vitamin C group. The average histopathological grade of the vitamin C group was significantly lower than the average histopathological grade of sham and β-hCG groups. The ratio of the testicular atrophy of the Vitamin C + β-hCG group (100%) was higher than sham (40%) and β-hCG (40%) groups with a significant difference. A significant statistical difference was found among all groups histopathological grades of testicular tissue., Conclusion: In animals taking vitamin C, an improvement of histopathological findings and a significant decrease in histological stages has been provided. However, it was observed that the histological findings of β-hCG and β-hCG + vitamin C groups worsened. It was found that β-hCG increased oxidative damage in the testicles and this damage can be so severe that exceeding the capacity of potent antioxidants such as Vitamin C. We believe that β-hCG can be harmful to testicles exposed to oxidative damage., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Testicular torsion during infancy (<1 year) is known to be a rare event with relatively few studies on the subject in the published scientific literature. We reviewed the experience of infant scrotal exploration within a paediatric surgical network of four centres serving an approximate paediatric population of 1.8 million., Aim: To review current practice of scrotal explorations in infancy and explore areas for improvement., Method: Retrospective review of emergency operations for acute scrotum between January 2016 and December 2018. Data are presented as median (range) and compared using non-parametric tests. P < 0.05 was regarded as significant., Results: A total of 560 paediatric scrotal explorations were performed. Of these, 25 (4%) were under one year at the time of surgery, median 4 months (1 day-5 months) (Fig. 1). The most common diagnosis was "epididymitis" (11/25, 44%). Testicular torsion was found in 28% (7/25), increasing to 66% (4/6) in those under one month. Of those with confirmed testicular torsion, three (43%) underwent a primary orchiectomy with contralateral fixation and three (43%) detorsion and bilateral fixation, with all three cases found to have testicular atrophy at follow-up. The final case was of metachronous torsion, with the initial presentation not operated on and the subsequent presentation undergoing detorsion and fixation. This was the only case of testicular salvage in our series. There were no underlying urological issues in any patient and no reported complications or ongoing urological issues post-surgery. The rate of follow-up was 17/25 (68%)., Conclusion: We present one of the only clinical series to focus on acute scrotum in the under one year old and not just the neonatal period. Testicular torsion remains a rare event in this age group but invariably leads to testicular loss., Competing Interests: Conflicts of interest None., (Copyright © 2021 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Preserving the spermatogonial stem cells (SSCs) in long periods of time during the treatment of male infertility using stem cell banking systems and transplantation is an important issue. Therefore, this study was conducted to develop an optimal cryopreservation protocol for SSCs using 10 mM pentoxifylline (PTX) as an antioxidant in basal freezing medium. Testicular torsion-a mouse model for long-term infertility-was used to transplant fresh SSCs (n = 6), fresh SSCs treated with PTX (n = 6), cryopreserved SSCs with basal freezing medium (n = 6), and cryopreserved SSCs treated with PTX (n = 6). Eight weeks after germ cell transplantation, samples were assessed for proliferation, through evaluation of Ddx4 and Id4 markers, and differentiation via evaluation of C-Kit and Sycp3, Tnp1, Tnp2, and Prm1 markers. According to morphological and flow cytometry results, SSCs are able to form colonies and express Gfra1, Id4, α6-integrin, and β1-integrin markers. We found positive influence from PTX on proliferative and differentiative markers in SSCs transplanted to azoospermic mice. In the recipient testis, donor SSCs formed spermatogenic colonies and sperm. Respecting these data, adding pentoxifylline is a practical way to precisely cryopreserve germ cells enriched for SSCs in cryopreservation, and this procedure could become an efficient method to restore fertility in a clinical setup. However, more studies are needed to ensure its safety in the long term., (© 2021. Society for Reproductive Investigation.)