New insights about the early diagnosis of fertility impairment in varicoceles: the DNA repair gene example

Abstract

Of all men consulted for infertility, around 30% appear to have a varicocele, therefore, this male dysfunction has been considered as a potential cause of infertility in many patients. Emerging studies point out spermatozoa progressive motility as the most important predictor of fertility provided that the analysis was carried out with infertility duration, thus leaving unsolved problem to evaluate the spontaneous testicular damage during the very early phase in varicoceles. Given the deterioration of testicular function caused by varicoceles is progressive, the early and efficient evaluation of testicular damage would be of great importance for the future medical intervention in this population. The resultant mechanism by which varicoceles affect testicular function remains unclear, but the increase in testicular temperature is most commonly accepted aetiology. In this context, we hypothesize that metastasis-associated protein 1 (MTA1), an intrinsic DNA damage response component, possessing transient protective effect in primary spermatocytes against heat stress, bears the potential to be a diagnostic biomarker for the assessment of early testicular damage in varicoceles. The facet that the decrease of MTA1 expression appears much earlier than the beginning of apoptotic wave after heat stress warrants its theoretical rationality and technical accessibility for biochemical application. Basically, MTA1 participates in the maintenance of early apoptotic balance induced by hyperthermal stimulation by elevating the deacetylation level of p53, a master regulator responsible for the initial phase of germ cell apoptosis induced by hyperthermia. These knowledges collectively promote our belief that information from future experiments designed to further study MTA1 during spermatogenesis will provide a scientific basis for the development of a novel biomarker for early diagnosis of testicular detriment in varicoceles, which should lead to improved outcomes in this progressive pathology.