Celik-Ozenci C, Kuscu N, Gungor-Ordueri N E, Tasatargil A, Sahin P, Durmus H
Department of Histology and Embryology, Akdeniz University School of Medicine, Antalya, Turkey.
Department of Histology and Embryology, Biruni University School of Medicine, Istanbul, Turkey.
Andrology. 2017 Mar;5(2):362-369. doi: 10.1111/andr.12305. Epub 2016 Dec 19.
Varicocele is ordinarily accompanied by testicular damage and male infertility. Several theories have been proposed to explain the detrimental effect of varicocele on testis tissue, including the possible effects of oxidative stress. The poly(ADP-ribose) polymerase (PARP) pathway has been established as a major downstream intracellular pathway of oxidative stress. Recently we have reported that PARP pathway has been activated in varicocele-induced rat testicular damage model. The aim of the present study was to investigate the possible protective effect of PARP inhibition in varicocele-associated testicular damage. Fifty male Wistar rats were divided into five groups: control, sham, varicocele-induced, varicocele-induced 1,5-isoquinolinediol (ISO, a PARP inhibitor)-treated, and ISO treated groups. The ISO-treated rats received intraperitoneal injections of 3 mg/kg ISO daily for 13 weeks. After 13 weeks of varicocele induction, body and testes weights were investigated in all groups. Histopathology of testes were evaluated by light microscopy. Expressions of PAR, p53 and cytochrome c were detected by immunohistochemistry and cleaved PARP-1, PAR, p53 and cytochrome c by western blot. The degree of apoptosis was determined by TUNEL. Light microscopy revealed testicular damage comprising various degrees of seminiferous tubule degeneration in varicocele-induced rats and their testes weights decreased significantly, whereas ISO administration prevented it. Expressions of cleaved PARP-1, PAR, cytochrome c, and p53 increased significantly in varicocele-induced rats, whereas the level of these molecules were similar to controls in varicocele-induced rats treated with ISO. In conclusion, increased PARP activation in testes seems to be related with testicular damage and apoptosis associated with varicocele and pharmacological inhibition of this pathway might be an effective intervention to prevent varicocele-induced testicular injury.
精索静脉曲张通常伴有睾丸损伤和男性不育。人们提出了几种理论来解释精索静脉曲张对睾丸组织的有害影响，包括氧化应激的可能作用。聚（ADP - 核糖）聚合酶（PARP）途径已被确立为氧化应激的主要细胞内下游途径。最近我们报道，在精索静脉曲张诱导的大鼠睾丸损伤模型中PARP途径被激活。本研究的目的是探讨PARP抑制在精索静脉曲张相关睾丸损伤中的可能保护作用。五十只雄性Wistar大鼠被分为五组：对照组、假手术组、精索静脉曲张诱导组、精索静脉曲张诱导并用1,5 - 异喹啉二醇（ISO，一种PARP抑制剂）处理组和ISO处理组。经ISO处理的大鼠每天腹腔注射3mg/kg ISO，持续13周。精索静脉曲张诱导13周后，对所有组的体重和睾丸重量进行了研究。通过光学显微镜评估睾丸的组织病理学。通过免疫组织化学检测PAR、p53和细胞色素c的表达，通过蛋白质印迹法检测裂解的PARP - 1、PAR、p53和细胞色素c。通过TUNEL法测定凋亡程度。光学显微镜显示，精索静脉曲张诱导的大鼠睾丸损伤包括不同程度的生精小管变性，其睾丸重量显著下降，而给予ISO可预防这种情况。在精索静脉曲张诱导的大鼠中，裂解的PARP - 1、PAR、细胞色素c和p53的表达显著增加，而在用ISO处理的精索静脉曲张诱导的大鼠中，这些分子的水平与对照组相似。总之，睾丸中PARP激活增加似乎与精索静脉曲张相关的睾丸损伤和凋亡有关，对该途径的药理学抑制可能是预防精索静脉曲张诱导的睾丸损伤的有效干预措施。
