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Vitamin D3 Prevents the Deleterious Effects of Testicular Torsion on Testis by Targeting miRNA-145 and ADAM17: In Silico and In Vivo Study.

ABSTRACT: Testicular torsion (TT) is the most common urological emergency in children and young adults that can lead to infertility in many cases. The ischemia-reperfusion (IR) injury due to TT has been implicated in the pathogenesis of testicular damage. The main pathological mechanisms of contralateral injury after ipsilateral TT are not fully understood. In the presented study, we investigated the molecular and microscopic basis of ipsilateral and contralateral testicular injury following ipsilateral testicular torsion detorsion (T/D) and explored the possible protective role of vitamin D3. The biochemical analysis indicated that IR injury following T/D significantly decreased the activity of testicular glutathione peroxidase (GPx) enzyme, level of serum testosterone, serum inhibin B, and expression of testicular miRNA145, while increased the activity of testicular myeloperoxidase (MPO) enzyme, level of testicular malondialdehyde (MDA), level of serum antisperm-antibody (AsAb), and expression of ADAM-17. The histological and semen analysis revealed that torsion of the testis caused damages on different tissues in testis. Interestingly, administration of vitamin D3 prior to the IR injury reversed the deterioration effect of IR injury on the testicular tissues as indicated by biochemical and histological analysis which revealed normal appearance of the seminiferous tubules with an apparent decrease in collagen fiber deposition in both ipsilateral and contralateral testes. Our results revealed that the protective effect of vitamin D3 treatment could be attributed to target miRNA145 and ADAM17 protein. To further investigate these findings, we performed a detailed molecular modelling study in order to explore the binding affinity of vitamin D3 toward ADAM17 protein. Our results revealed that vitamin D3 has the ability to bind to the active site of ADAM17 protein via a set of hydrophobic and hydrophilic interactions with high docking score. In conclusion, this study highlights the protective pharmacological application of vitamin D3 to ameliorate the damages of testicular T/D on the testicular tissues via targeting miRNA145 and ADAM17 protein.

SUBMITTER: Mohamed DI

PROVIDER: S-EPMC8703569 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:INTRODUCTION:In testicular torsion, ischemia time from pain onset impacts testicular salvage. A tunica albuginea fasciotomy to relieve compartment pressure followed by a tunica vaginalis flap (TVF) may enhance salvage. OBJECTIVE:To define the optimal window of ischemia time during which TVF may be most beneficial to avoid orchiectomy. STUDY DESIGN:A retrospective cohort study of males presenting with testicular torsion at a single tertiary-care institution from January, 2003 to March, 2017. Ischemia time was defined as duration of pain from onset to surgery. Because TVF would be an option to orchiectomy, and it was found that ischemia time was longer in testicles that underwent orchiectomy, matching was performed. Cases of torsion treated with TVF were matched 1:1 with cases treated with orchiectomy on age at surgery, and ischemia time. Outcomes included postoperative viability, defined as palpable testicular tissue with normal consistency, and atrophy, defined as palpable decrease in size relative to contralateral testicle. Sensitivity analyses were performed restricting to the subgroups with postoperative ultrasound, >6 months' follow-up, and additionally matching for degrees of twist. RESULTS:A total of 182 patients met eligibility criteria, of whom 49, 36, and 97 underwent orchiectomy, TVF, and septopexy alone, respectively. Median follow-up was 2.7 months; 26% of patients had postoperative ultrasound (61% of TVF group). In the orchiectomy, TVF, and septopexy groups, respectively, median ischemia times were 51, 11, and 8 h, postoperative viability rates were 0, 86, and 95%, and postoperative atrophy rates were 0, 68, and 24%. After matching, 32 patients with TVF were matched to 32 patients who underwent orchiectomy. In the TVF group, postoperative viability occurred in 95% (19/20) vs 67% (8/12) of patients with ischemia times ?24 and >24 h, respectively. Atrophy occurred in 67% (12/18) vs 83% (10/12) of these same respective patients. Sensitivity analysis by ultrasound and longer follow-up found similar viability results, although atrophy rates were higher. Additional matching for degrees of twist showed lower viability and higher atrophy rates for increasing ischemia times. DISCUSSION:Patients who presented with testicular torsion with ischemia times ?24 h and who were being considered for orchiectomy may have benefitted most from TVF, albeit at high risk of atrophy. However, for ischemia times >24 h, TVF may still have preserved testicular viability in two-thirds of cases. A limitation was short follow-up. CONCLUSION:A TVF was a valid alternative to orchiectomy for torsed testicles, albeit with high testicular atrophy rates.

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Vitamin D3 Prevents the Deleterious Effects of Testicular Torsion on Testis by Targeting miRNA-145 and ADAM17: In Silico and In Vivo Study.

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