A global view of the pathophysiology of varicocele

Abstract

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.

Signs of ROS-Associated Autophagy in Testis and Sperm in a Rat Model of Varicocele

“…This resulted in a decrease of the cell antioxidant capacity [18,38,39]. In addition, testicular hyperthermia associated with VCL also contributes to shift the AO/ROS balance towards oxidative stress [20,40]. We are here in total agreement with the literature since we have observed that in the VCL group, all the major primary AO activities (SOD, CAT & GPX) were reduced and that the tissue MDA content was significantly increased signing a clear state of oxidative stress.…”

“…Since oxidative stress, heat stress, and hypoxia are the main factors involved not only in the pathophysiology of varicocele [20] but also in the induction of autophagy [21,22], we have sought to understand the relationship between autophagy and varicocele. The aim of this study was to create an experimental model of varicocele in rats to highlight the role of autophagy in VCL testicular tissue and sperm.…”

The Importance of Oxidative Stress in Determining the Functionality of Mammalian Spermatozoa: A Two-Edged Sword

“…Another situation in which raised intratesticular temperature is evident is varicocele. This condition is also known to be associated with a loss of sperm function and DNA integrity as a consequence of oxidative stress [100,101]. Surgical ligation of the left internal spermatic vein to correct the varicosity has been shown to reduce oxidative stress parameters and to improve sperm quality and the concomitant administration of antioxidants has been shown to facilitate this process [102,103].…”

Varikosel patofizyolojisi 2019

“…[4] Bu mekanizmalar; hipertermi, hipoksi, toksik sürrenal metabolitlerin reflüsü, hipogonadizm ve kadmium birikmesi olarak bildirilmektedir. [4,5] Ancak, bu patofizyolojik mekanizmaların hangi moleküler ve alt etkileşim mekanizmalar ile etkili olduğu halen araştırma konularıdır. [5] Güncel olarak varikoselin infertilite üzerine patofizyolojik etkisi çeşitli etyolojik faktörlerin kombine etkileşimi ile ortaya çıkmaktadır.…”