Apoptosis in testicular germ cells

摘要

Onset of speimatogenesis is associated with an apoptosis wave that limits its efficiency during the first cycles in most mammals Beyond the fust cycles the actual efficiency of spermatogenesis remains always under the theoretical one Such physiological apoptosis depends partly upon the relationships between germinal cells and Sertoli cells Since the steps of spermatogenesis require a continuous progression of the cell cycle rather than any arrest, germ cells might therefore be more sensitive to apoptosis. Moreover, this may lead to severe disturbances between proliferation and cell death The first experiments designed to understand the mechanisms of germ cell apoptosis were based on hormonal deprivation or cryptorchidism However, the link between hormonal or cellular action and cell survival remained to be established The involvement of bcl-2 family genes has been confirmed, whereas the place of Fas/Fas ligand system during the first cycles of spermatogenesis remains a matter of debate Factors involved in Tumor Necrosis Factor (TNF)/TNF Rl are under study Among the oncogenes, which may modulate the apoptotic process, Kit/Stem Cell Factor has a peculiar interest, since Kit is expressed in germ cells to some extent and Leydig cells, whereas SCF is expressed in Sertoli cells. Using a transgenic mice model where Kit gene was inactivated by the insertion of a nls-lacZ sequence in its first exon, we showed that one single copy of the gene was unable to sustain at a physiological level both spermatogenesis and fertility in the male mice. Finally, the analysis of the signal transduction pathways involved in testicular apoptosis and their mechanisms of control are key steps in understanding both the impairment of spermatogenesis and the genesis of some germ cell tumours.