Varicocele and male infertility: Part II: Pathophysiology of varicoceles in male infertility

Abstract

Varicoceles are found in 19 to 41% of infertile men, and is one treatable form of male infertility. The mechanism by which varicoceles cause the variable effect on male infertility and spermatogenesis is still unknown. Experimental animal models play a useful (but limited) role due to the sudden and variable iatrogenic nature of the varicoceles and the duration of the studies. Much of the human data are derived by the characterization of associated differences in measurable parameters between men with and without varicoceles. The role of hyperthermia, testicular blood flow and venous pressure changes, reflux of renal/adrenal products, hormonal dysfunction, autoimmunity, defects in acrosome reaction, and oxidative stress, in the pathophysiology of varicocele will be discussed.

Is it worthwhile to operate on subclinical right varicocele in patients with grade II–III varicocele in the left testicle?

“…The exact mechanism by which an incidental varicocele becomes pathological remains unclear (29). Recently, studies have demonstrated the role of oxidative stress in men with varicocele and infertility (30).…”

“…A number of studies have looked for specific markers of testicular injury in infertile men with clinical varicoceles (29). Even though Dubin and Hotchkiss have described specific findings of germinal cell hypoplasia and premature sloughing of immature forms within the lumena of the seminiferous tubules in their study of 88 subfertile men with varicoceles, most of the reported changes in testicular histology and semen quality seen in these men are largely nonspecific (32).…”

“…Even though Dubin and Hotchkiss have described specific findings of germinal cell hypoplasia and premature sloughing of immature forms within the lumena of the seminiferous tubules in their study of 88 subfertile men with varicoceles, most of the reported changes in testicular histology and semen quality seen in these men are largely nonspecific (32). Varicoceles not only have deleterious effects on the hormonal aspects of spermatogenesis but also in decreased function through testicular hyperthermia, reflux of toxic metabolites and seminiferous tubular hypoxia secondary to venous stasis (3,29). Since in our series of patients no differences in the hormonal levels were found between patients with and those without right subclinical varicoceles when a clinical left grade II-III varicocele was present, we argue that a subclinical varicocele does not impaired hormonal levels.…”

An association between sperm PLCζ levels and varicocele?

“…In addition to thermoregulatory failure, hypoxia due to venous stasis, high levels of oxidants, anti-sperm antibodies, reflux of renal and adrenal metabolites down the spermatic vein, and dilution of intra-testicular substrates, such as testosterone, were proposed to explain impairments in testicular function resulting from varicocele [27,28]. However, to gain more insight into molecular pathology of varicocele, evaluation of various metabolites, transcripts, and proteins in sperm may pave the way for better understanding the molecular pathology of varicocele.…”

Expression of the Fas-ligand gene in ejaculated sperm from adolescents with and without varicocele

“…The incidence of varicocele in the general adult population is about 15-20%, and it can be considered a major cause of male infertility. Although they probably originate due to valvular absence or incompetence in the internal spermatic veins, varicoceles may occur due to a number of different mechanisms, and is thus considered a multifactorial disease [1,2].…”