KIT-LIGAND MEDIATES SURVIVAL OF TYPE-A SPERMATOGONIA AND DIVIDING SPERMATOCYTES IN POSTNATAL MOUSE TESTES

In the mouse testis, spontaneous death of spermatogonia has a large im pact on the output of differentiating spermatids. The tyrosine kinase receptor c-kit is expressed in type A, intermediate, and B spermatogon ia, and kit-ligand (KL) is expressed in Sertoli cells. Previous work i ndicated a depletion of type A spermatogonia after in vivo exposure to an antibody that blocks c-kit function. The present work was undertak en to determine whether blocking c-kit function results in apoptosis o f spermatogonia or in an inability of spermatogonia to proliferate. Te stes sections were stained by a method that detects apoptotic cells in situ. In testes of 8-day postnatal (P8) males, type A spermatogonia ar e the predominant germ cell type present. Stained sections from P8 mal es injected with the c-kit antagonistic antibody ACK2 showed a fivefol d higher rate of cell death than uninjected controls. At least a twofo ld increase was observed in P12 and P30 injected males and in P30 SId/ + males as compared to uninjected controls. Determination of the stage of germ cell development that was affected in P30 males indicated tha t the frequency of genial cell death was increased fourfold, but the f requency of death in spermatocytes around the time of the meiotic divi sion was increased 15-fold. It is concluded that KL acts to prevent ap optosis in the testis in vivo, that the membrane bound form of KL may be more effective, and that survival of late meiotic and dividing sper matocytes is regulated by KL through an indirect mechanism probably me diated by Sertoli cells. Thus, KL is an important regulator of spermat id output. (C) 1995 Wiley-Liss, Inc.