This article is available online at http://www.jlr.org motherapeutic drugs and X-ray irradiation. Precisely because of its effi cacy to kill rapidly dividing cells, exposure of the testis to these agents, whether incidental or therapeutic, selectively targets the population of spermatogenic cells and is a potential cause of male infertility. While somatic cells, including Sertoli cells, are apparently unaffected, spermatogonia that are mitotically dividing and spermatocytes during the early phases of meiosis are the testicular cells most vulnerable to X-rays ( 1 ). Relatively less susceptible are nondividing spermatogonial stem cells on the one hand and postmeiotic cells on the other. Spermatids and spermatozoa, with their much more compact nuclei, are notably resistant. Germ cell death induced by X-ray irradiation mostly occurs via apoptosis ( 2, 3 ), which results from radiation-induced free radical generation damaging DNA. The protein P53, the known intracellular sensor of DNA damage, is required for this response ( 1, 4 ). P53 upregulates in germ cells the production of Fas, the surface receptor that, on binding the Fas ligand produced by Sertoli cells, activates apoptosis via a caspase-mediated cascade ( 5, 6 ).A few weeks after having locally irradiated the testis with X-rays, spermatogenesis recommences from type A spermatogonial stem cells that had not been affected at irradiation time in some mammalian species like mice ( 1 ) but not in others like LBNF1 rats, which are in this regard a good model of the human testicular sensitivity to X-rays ( 7 ). In these rats, despite the presence and normal proliferation of apparently undamaged type A spermatogonia, it is their further differentiation that is after some time impeded, The mammalian testis is known to be highly susceptible to a variety of anticancer agents, including a number of che-
This work was supported by funding from Consejo Nacional de Investigaciones Científi cas y Técnicas (CONICET), Agencia Nacional de Promoción de la Ciencia y la Tecnología (ANPCyT), and Universidad Nacional del Sur (UNS).