Role of c-kit in mammalian spermatogenesis

The tyrosine-kinase receptor c-kit and its ligand, stem cell factor (SCF), are essential for the maintenance of primordial germ cells (PGCs) in both s exes. However, c-kit and a postmeiotic-specific alternative c-kit gene prod uct play important roles also during post-natal stages of spermatogenesis. In the adult testis, the c-kit receptor is re-expressed in differentiating spermatogonia, but not in spermatogonial stem cells, whereas SCF is express ed by Sertoli cells under FSH stimulation. SCF stimulates DNA synthesis in type A spermatogonia cultured in vitro, and injection of anti-c-kit antibod ies blocks their proliferation in vivo. A point mutation in the c-kit gene, which impairs SCF-mediated activation of phosphatydilinositol 3-kinase, do es not cause any significant reduction in PGCs number during embryonic deve lopment, nor in spermatogonial stem cell populations. However males are com pletely sterile due to a block in the initial stages of spermatogenesis, as sociated to abolishment of DNA-synthesis in differentiating A(1)-A(4) sperm atogonia. With the onset of meiosis c-kit expression ceases, but a truncate d c-kit product, tr-kit, is specifically expressed in post-meiotic stages o f spermatogenesis, and is accumulated in mature spermatozoa. Microinjection of tr-kit into mouse eggs causes their parthenogenetic activation, suggest ing that it might play a role in the final function of the gametes, fertili zation. (J, Endocrinol. Invest. 23: 609-615, 2000) (C) 2000. Editrice Kurti s.