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 impact on the output of differentiating spermatids. The tyrosine kinase receptor c-kit is expressed in type A, intermediate, and B spermatogonia, and kit-ligand (KL) is expressed in Sertoli cells. Previous work indicated a depletion of type A spermatogonia after in vivo exposure to an antibody that blocks c-kit function. The present work was undertaken to determine whether blocking c-kit function results in apoptosis of spermatogonia or in an inability of spermatogonia to proliferate. Testes sections were stained by a method that detects apoptotic cells in situ. In testes of 8-day postnatal (P8) males, type A spermatogonia are the predominant germ cell type present. Stained sections from P8 males injected with the c-kit antagonistic antibody ACK2 showed a fivefold higher rate of cell death than uninjected controls. At least a twofold 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 that the frequency of gonial cell death was increased fourfold, but the frequency of death in spermatocytes around the time of the meiotic division was increased 15-fold. It is concluded that KL acts to prevent apoptosis in the testis in vivo, that the membrane bound form of KL may be more effective, and that survival of late meiotic and dividing spermatocytes is regulated by KL through an indirect mechanism probably mediated by Sertoli cells. Thus, KL is an important regulator of spermatid output.
Packer
A I
AI
Department of Cell Biology and Anatomy, Cornell University Medical College, New York, NY 10021, USA.
Besmer
P
P
Bachvarova
R F
RF
D000818:Animals; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis; D002470:Cell Survival; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology / Q000502:physiology*; D013090:Spermatocytes / Q000502:physiology*; D013093:Spermatogonia / Q000502:physiology*; D019089:Stem Cell Factor / Q000502:physiology*; D013737:Testis / Q000166:cytology*
D000906:Antibodies; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit