Testicular Cancer

Abstract

A variety of epidemiological clues suggest that testicular cancer may be caused by the disruption of early testis development by exposure to xenobiotic chemicals. Although there is little direct evidence linking chemical exposures and germ cell cancers, the possible direct impact and interactions between the changing environment and the genome, and the likelihood of resulting epigenetic heritable changes, are beginning to be explored. Most of the available evidence in humans comes from the occurrence of cryptorchidism, but as this developmental disorder is a considerable risk factor for the development of testicular cancer, it is plausible that both disorders may share a common etiology and pathogenesis. Indeed, limited experimental evidence in rabbits shows that developmental exposure to certain toxicants results in impaired testicular descent as well as carcinoma in situ (CIS)-like atypical germ cells. The major impediment in the study of human testicular germ cell cancers is the lack of suitable animal models. Recent studies suggest that rabbits and dogs might be excellent models to investigate human testicular cancer. Rabbits manifest CIS-like lesions (the precursor of classical seminomas) and dogs spontaneously manifest a relatively high incidence of germ cell tumors, most of which are thought to be equivalent of human spermatocytic seminomas. Any advances in our understanding of human germ cell cancers have arisen from the identification of transformed gonocytes as the likely precursors of the most common testicular neoplasms. Such advances have resulted from efforts to integrate knowledge of (1) the signaling pathways and mechanisms that govern key steps in the differentiation and maturation of testicular cells, (2) the effects of toxicants on these processes, and (3) the common and species-specific features of normal and disordered testicular growth. Studies using molecular markers indicate that testicular development and differentiation rely on conserved molecular mechanisms, so information gained from examining nonhuman species is useful for understanding human testicular cancer. Herein, several of these facets are briefly reviewed and discussed.