2.1.4. Varicocele

Varicocele is a pathology associated with an abnormal enlargement of the pampiniform venous plexus surrounding the spermatic cord in the scrotum [39]. This clinical condition occurs in approximately 15% of males and accordingly represents the most common cause of primary and secondary infertility in men; accounting for as much as 40% of all cases of male infertility [40]. Consistent with this clear association between varicocele and male infertility, a considerable body of evidence supports OS as a key causative agen<sup>t</sup> in the pathophysiology of varicocele [41]. Indeed, both infertile patients and fertile men with varicocele frequently present with higher levels of ROS, NO, and lipid peroxidation products in their reproductive tract than men without varicocele [42–46]. The most widely accepted model to account for these findings suggests that varicoceles lead to an increase in scrotal temperature owing to the reflux and accumulation of warmed abdominal blood within the pampiniform plexus. The resultant heat stress has, in turn, been postulated to enhance ETC electron leakage via thermal inhibition of mitochondrial complexes, thus accentuating mitochondrial ROS production (reviewed in [47]).

### **3. Exogenous Sources of ROS**

In addition to endogenous influences, modern lifestyle and environment factors have also been increasingly linked with a range of adverse health sequelae, including poorer quality semen parameters. Below, we give brief consideration to physical and chemical factors that have been associated with heightened levels of seminal ROS.
