Male infertility: a risk factor for testicular cancer

Male infertility lies at the crossroads of genetic determinants and environmental effects. Although the exact genetic mechanisms of male infertility are still unclear, this disorder is associated with a host of medical diseases, including testicular cancer. Testicular dysgenesis syndrome, the Hiwi protein and chromosome 12 aneuploidy, DNA mismatch repair, and Y-chromosome instability have been postulated as possible connections between male infertility and testicular germ cell tumor (TGCT). The advent of assisted reproductive technology has allowed men to bypass evaluation by a urologist with expertise in infertility at a time when semen quality seems to be decreasing in parallel with an increasing incidence of TGCT in industrialized nations. Advances in epigenetics, the sequencing of the human genome and maturation of large datasets from countries with centralized medical records are heralding a new era of genetic medicine in this field. The exquisite sensitivity of the germinal epithelium to changes in the external environment and the internal metabolic profile present an excellent opportunity to explore the interaction between infertility and TGCT. The elucidation of the pathways underlying this association will enable development of appropriate tests that will identify men susceptible to development of TGCT and other testicular pathologies.