Department of Andrology and Sexology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Andrology. 2018 Sep;6(5):654-661. doi: 10.1111/andr.12511. Epub 2018 Jul 6.
Varicocele is the most common abnormality identified in men being evaluated for subfertility. In this comprehensive review of the pathophysiology of varicocele, we will shed light on novel pathophysiological findings and their clinical implications that may direct future researches; we will shed light on the impact of transient scrotal hyperthermia and the roles of inflammation and differential protein expression and androgen expression in spermatozoa on inducing pathophysiological findings. Furthermore, we will clarify the linked processes contributing to the pathophysiology of varicocele and the impact of genetics on the induction of these processes. Spermatogenesis is a temperature-sensitive process, and heat stress of varicocele is considered the most plausible cause of impaired spermatogenesis. The three processes associated with the presence of varicocele - heat stress, excess reactive oxygen species, and increased apoptosis - appear to be linked; heat stress is associated with increased levels of reactive oxygen species and oxidative stress, which can induce apoptosis. The genetic role should not be overlooked as a contributing factor in the induction of heat stress, excess reactive oxygen species/oxidative stress, and apoptosis; this is evidenced by the association of varicocele with decreased expression of heat-shock proteins, higher polymorphism of glutathione S transferase and nitric oxide synthase genes, and increased BAX and decreased BCL2 genes and proteins. In this article, we will highlight the need of application of novel diagnostic techniques that can provide a precise pathophysiological diagnosis to guide potential specific innovative therapies. Innovative therapies can counteract the varicocele-induced stasis, suppress the degenerative effects of testicular hyperthermia, reduce the varicocele-induced apoptosis, and target the elevated-neutrophil products aiming at abrogating the testicular damage caused by the induced varicocele in rats/mice. In conclusion, on the basis of the novel scientific research, it may be possible to formulate new treatments and achieve the appropriate selection of patients who can benefit from these treatments.
精索静脉曲张是男性不育评估中最常见的异常。在对精索静脉曲张病理生理学的全面综述中，我们将阐明新的病理生理发现及其临床意义，这些发现可能指导未来的研究；我们将阐明短暂阴囊过热的影响以及炎症和差异蛋白表达和雄激素表达在精子中诱导病理生理发现的作用。此外，我们将阐明导致精索静脉曲张病理生理学的相关过程以及遗传因素对这些过程诱导的影响。精子发生是一个对温度敏感的过程，精索静脉曲张的热应激被认为是导致精子发生受损的最合理原因。与精索静脉曲张存在相关的三个过程——热应激、过多的活性氧物质和增加的细胞凋亡——似乎是相关的；热应激与活性氧物质和氧化应激水平的增加有关，这可能会诱导细胞凋亡。遗传作用不应被忽视为诱导热应激、活性氧物质/氧化应激和细胞凋亡的一个因素；精索静脉曲张与热休克蛋白表达降低、谷胱甘肽 S 转移酶和一氧化氮合酶基因的多态性增加以及 BAX 增加和 BCL2 基因和蛋白减少有关，这证明了这一点。在本文中，我们将强调需要应用新型诊断技术，以提供精确的病理生理学诊断，从而指导潜在的特定创新治疗。创新性疗法可以对抗精索静脉曲张引起的停滞，抑制睾丸过热的退行性影响，减少精索静脉曲张引起的细胞凋亡，并针对升高的中性粒细胞产物进行靶向治疗，以消除精索静脉曲张引起的睾丸损伤在大鼠/小鼠中。总之，基于新的科学研究，可能制定新的治疗方法，并实现对可以从这些治疗中受益的患者的适当选择。
