TNF alpha down-regulates the Fas ligand and inhibits germ cell apoptosis in the human testis

The cytokine TNF alpha is known to be secreted by testicular germ cells. Ho wever, its effect on maturing germ cells is unknown, and its role in the re gulation of spermatogenesis is unclear. Here we aimed at characterizing the effects of TNF alpha on germ cell survival in the human testis. We found t hat TNF alpha effectively and dose-dependently inhibited germ cell apoptosi s, which was induced in vitro by incubating segments of human seminiferous tubules under serum-free culture conditions. EMSAs indicated increased acti vity of nuclear factor kappaB in seminiferous tubules cultured under apopto sis-inducing conditions. However, we did not observe any significant effect of TNF alpha on the activation of this transcription factor, which is ofte n considered to be a mediator of TNF alpha -induced survival signals. As th e expression of the TNF receptor protein in the human seminiferous epitheli um was predominantly found in the Sertoli cells, the antiapoptotic effect o f TNF alpha is probably mediated via these somatic cells. Interestingly, ex pression of the Fas ligand, a known inductor of testicular apoptosis, was d own-regulated by TNF alpha. Thus, in the seminiferous tubules, germ cell-de rived TNF alpha may regulate the level of the Fas ligand and thereby contro l physiological germ cell apoptosis.