Article DAMAGE TO FERTILITY BY CANCER AND ITS TREATMENTS Mechanisms of Toxic Damage to Spermatogenesis

Azoospermia and long-lasting testicular atrophy are common adverse consequences of cancer treatment. Chemotherapeu-tic agents may disrupt spermatogenesis by targeting various testicular cell types (Leydig cells, Sertoli cells, and germ cells) and by activating numerous molecular pathways involved in germ cell life-and-death decision making. Genetically modi-fi ed animal models with defi ciencies in specifi c proapoptotic and prosurvival pathways have become powerful tools in understanding the molecular regulation of spermatogenesis and the response of the seminiferous epithelium to toxic injury. In this brief review, selected examples of results of toxic exposures in genetically defi cient animal models are dis-cussed to highlight the roles of p53 and the Fas system as modulators of proapoptotic activity in the testis. A fi nal section focuses on cisplatin, a cancer chemotherapeuti