Varicocele and male infertility: Part II - The pathophysiology of varicoceles in the light of current molecular and genetic information

Varicoceles are a common cause of male infertility, but despite data being obtained from animal models and human studies the pathophysiology remains u nclear. Recently, molecular and genetic information has been reported on me n with varicoceles which may shed new light onto the causes of decreased se men parameters and poor sperm function. Here, a number of studies are revie wed in an attempt to develop a working hypothesis for the relationship of v aricoceles and infertility. New studies on testicular tissue of men with va ricoceles have demonstrated increased apoptosis among developing germ cells , which may be the cause of oligospermia. Other studies with semen have sho wn increased levels of reactive oxygen species (ROS) in association with po or sperm motility. Recent studies of morphologically abnormal spermatozoa h ave demonstrated disruption of the sperm head actin by cadmium, a cation re ported to be present in high concentrations among some men with varicoceles . Finally, microdeletions of the alpha-1 subunit of the sperm calcium chann els in a proportion of men with varicoceles suggests a genetic defect leadi ng to abnormal acrosomal function. The intent of this review was to explain the pathophysiology of varicoceles, and the findings seem to support a 'co -factor' hypothesis. In order for varicoceles to be associated with inferti lity, they exist as 'co-factors' along with other molecular/genetic problem s.