The Fas system, a regulator of testicular germ cell apoptosis, is differentially up-regulated in Sertoli cell versus germ cell injury of the testis

Sertoli cells, the supportive cells in the seminiferous epithelium, orchest rate spermatogenesis by providing structural and nutritional support to ger m cells. In the rat, physiological apoptosis occurs continuously to limit t he size of the germ cell population to numbers that can be adequately suppo rted. This form of germ cell death is exaggerated after testicular insults such as toxicant treatment, radiation, and heat exposure. The Fas system ha s been proposed as a key regulator of the activation of germ cell apoptosis . According to this model, Fas ligand (FasL) and Fas, expressed by Sertoli cells and germ cells, respectively, respond to environmental conditions and initiate germ cell death. To assess the role of the Fas system in various testicular injury models, a semiquantitative RT-PCR technique was used to e valuate the expression kinetics of both Fast and Fas after induction of mas sive germ cell death. Radiation exposure, which targets actively dividing g erm cells, produced an up-regulation of Fas gene expression, but not Fast g ene expression. However, administration of mono-(2-ethylhexyl)phthalate and 2,5-hexanedione, two widely studied Sertoli cell toxicants, resulted in up -regulated expression of both Fast and Fas, These data support the followin g hypotheses: 1) up-regulation of Fas is a common and critical step for ini tiating germ cell death in vivo; and 2) if Sertoli cells are injured, Serto li cells up-regulate Fast to eliminate Fas-positive germ cells, which canno t be supported adequately.