The Hypoxic Testicle: Physiology and Pathophysiology

Abstract

Mammalian spermatogenesis is a complex biological process occurring in the seminiferous tubules in the testis. This process represents a delicate balance between cell proliferation, differentiation, and apoptosis. In most mammals, the testicles are kept in the scrotum 2 to 7°C below body core temperature, and the spermatogenic process proceeds with a blood and oxygen supply that is fairly independent of changes in other vascular beds in the body. Despite this apparently well-controlled local environment, pathologies such as varicocele or testicular torsion and environmental exposure to low oxygen (hypoxia) can result in changes in blood flow, nutrients, and oxygen supply along with an increased local temperature that may induce adverse effects on Leydig cell function and spermatogenesis. These conditions may lead to male subfertility or infertility. Our literature analyses and our own results suggest that conditions such as germ cell apoptosis and DNA damage are common features in hypoxia and varicocele and testicular torsion. Furthermore, oxidative damage seems to be present in these conditions during the initiation stages of germ cell damage and apoptosis. Other mechanisms like membrane-bound metalloproteinases and phospholipase A2 activation could also be part of the pathophysiological consequences of testicular hypoxia.

Hyperthermia and not hypoxia may reduce sperm motility and morphology following testicular hyperthermia

“…An in vivo model is preferred to understand testicular physiology, as there are autoprotective mechanisms against low O 2 tension in the testis (Elshaari et al 2012) and natural antioxidant systems (Aitken and Roman 2008;Reyes et al 2012) that are difficult or impossible to replicate in an in vitro model. Furthermore, under heat stress, testicular vasomotion (rhythmic tone variation in blood vessels) is greatly suppressed (Setchell et al 1995) which can impair testicular function (Lysiak et al 2000;Aalkjaer et al 2011).…”

Local Injection of Mesenchymal Stem Cells Protects Testicular Torsion-induced Germ Cell Injury

“…According to the clinical standard operation procedure, scrotal exploration and testicular detorsion will be arranged emergently if testicular torsion is suspected [1]. However, detorsion-induced I/R injury will superimpose the torsioninduced ischemic change on the testis [2][3][4]. To prevent further I/R injury, we prefer pretreatment with allogenic MSCs in the emergency room before surgical detorsion rather than after surgical detorsion.…”

“…apoptosis in germ cells [20]. It has already been established that torsion-detorsion increased the oxidative stress in testis which triggers apoptosis from the intrinsic pathway [2][3][4]. We further measured the oxidative stress by lipid peroxidation assay.…”

“…In addition, vascular endothelial cell injury and induction of microcirculation disorders during reperfusion are harmful to survival of the testis. Production of free radicals such as reactive oxygen species and nitric oxide make a vicious circle of I/R injury [2][3][4].…”

Resveratrol improves reproductive parameters of adult rats varicocelized in peripuberty

“…Therefore, the poor vascularization of the testicular tissue, typically occurred in varicocele, reduces oxygen rates, then compromising mitochondrial metabolism (Aitken & Roman 2008, Ferramosca et al 2015. As a consequence, an increase in reactive oxygen species (ROS) production may occur, which directly affects spermatogenesis (Naughton et al 2001, Reyes et al 2012) and increases germ cell apoptosis, necrosis and degeneration (Nasr Esfahani & Tavalaee 2012, Reyes et al 2012. Thus, in the characteristic pathological process of varicocele, male infertility and oxidative stress are closely linked (Hendin et al 1999, Miyaoka & Esteves 2012.…”