Department of Surgery, Division of Urology, Human Reproduction Section, Universidade Federal de São Paulo- UNIFESP, São Paulo, Brazil.
Department of Basic Science, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
Reprod Sci. 2023 Aug;30(8):2401-2415. doi: 10.1007/s43032-023-01200-4. Epub 2023 Feb 23.
Varicocele (VCL) has been shown to induce severe oxidative stress in the testicular tissue resulting in 35% of males with primary infertility. To compare the exacerbating impacts of varicose on oxidative DNA damage and homeostatic antioxidant reactions in the seminiferous tubules (ST), enclosed and far from varicose vessels. Thirty mature Wistar rats were divided into control and VCL-induced groups. To approve VCL, the testicular diameters, volume, and blood circulation were measured using B-mode and Doppler ultrasonography. Next, to confirm oxidative stress (OS), the global homeostatic antioxidant biomarkers were evaluated. Moreover, the OS-induced oxidative DNA damage and homeostatic antioxidant reactions were compared between STs nearby and far from varicose vessels. Finally, to clarify the DNA damage-induced impact on the cell cycle progression, the global and local expressions of Cyclin D1, Cdk4, and p21 were examined. The VCL-induced group exhibited diminished global antioxidant status (marked with TAC, GPX, SOD, and CAT) and UNG and MPG expression levels. Moreover, the cross-sections of the VCL group represented a prominent reduction in the UNG, MPG, Cyclin D1, and cdk4, and upregulation in the p21 expression levels, more prominently in the STs nearby varicose vessels. Concerning severe oxidative DNA damage and intensive molecular changes in the STs nearby the varicose vessels, they can be considered the main cause of oxidative DNA damage in enclosed tubules. Thus, the varicose-mediated oxidative DNA damage negatively impacts the cell cycle progression in the tubules more intensively in the subcapsular area.
精索静脉曲张（VCL）已被证实会在睾丸组织中引起严重的氧化应激，导致 35%的原发性不育男性。为了比较精索静脉曲张对生精小管（ST）中氧化 DNA 损伤和内稳态抗氧化反应的恶化影响，这些 ST 被包裹并远离曲张的血管。将 30 只成熟的 Wistar 大鼠分为对照组和 VCL 诱导组。使用 B 型和多普勒超声测量睾丸直径、体积和血液循环，以证实 VCL 的存在。接下来，评估全局内稳态抗氧化生物标志物，以确认氧化应激（OS）的存在。此外，比较了紧邻和远离曲张血管的 ST 之间 OS 诱导的氧化 DNA 损伤和内稳态抗氧化反应。最后，为了阐明 DNA 损伤对细胞周期进程的影响，检查了全局和局部 Cyclin D1、Cdk4 和 p21 的表达。VCL 诱导组表现出全局抗氧化状态（以 TAC、GPX、SOD 和 CAT 为标志）和 UNG 和 MPG 表达水平的降低。此外，VCL 组的横切面显示 UNG、MPG、Cyclin D1 和 cdk4 的明显减少，以及 p21 的表达水平上调，尤其是在紧邻曲张血管的 ST 中。鉴于紧邻曲张血管的 ST 中严重的氧化 DNA 损伤和强烈的分子变化，它们可以被认为是封闭小管中氧化 DNA 损伤的主要原因。因此，曲张介导的氧化 DNA 损伤在近包膜区域的小管中更强烈地影响细胞周期进程。
