Stem cell factor/c-kit system in spermatogenesis

One of the major unresolved questions with male infertility is the identifi cation of the molecular origin of a great majority of the spermatogenetic a rrests currently diagnosed as idiopathic male infertility During the past y ears, several families of regulating factors have been implicated in sperma togenesis defects observed essentially in animal models. Among these factor s are signalling molecules, and particularly the stem cell factor (SCF)/c-k it system. The SCF and its receptor c-kit are an appropriate example to ill ustrate the role of signalling molecules in the physiology and pathology of spermatogenesis, The SCF/c-kit regulates primordial germ cell migration, p roliferation and apoptosis during fetal gonadal development, The SCF/c-kit also regulates spermatogonia proliferation in the adult animal. Ln mutant m ice, abnormalities of the SCF/c-kit gene expression, such as gene deletion, point mutation, alternative splicing defect, lead to different types of sp ermatogenesis alterations (e.g. decrease in primordial germ cell migration, decrease in spermatogonia proliferation), More recently defects in SCF/c-k it gene expression have also been shown in human testicular dysfunctions, I ndeed, a reduction in SCF/c-kit expression has been evidenced in oligozoosp ermia/azoospermia associated with an increase in the germ cell apoptosis pr ocess. In addition, c-kit seems to be a good marker of seminoma testicular tumors, This review reports a large number of data-obtained essentially in animal models-that suggest an important role for the SCF/c-kit system in sp ermatogenesis and, as a corollary, its potential involvement in spermatogen ic defects.