Stem cell factor/c-kit system in spermatogenesis

One of the major unresolved questions with male infertility is the identification of the molecular origin of a great majority of the spermatogenetic arrests currently diagnosed as idiopathic male infertility During the past years, several families of regulating factors have been implicated in spermatogenesis defects observed essentially in animal models. Among these factors are signalling molecules, and particularly the stem cell factor (SCF)/c-kit system. The SCF and its receptor c-kit are an appropriate example to illustrate the role of signalling molecules in the physiology and pathology of spermatogenesis, The SCF/c-kit regulates primordial germ cell migration, proliferation and apoptosis during fetal gonadal development, The SCF/c-kit also regulates spermatogonia proliferation in the adult animal. Ln mutant mice, abnormalities of the SCF/c-kit gene expression, such as gene deletion, point mutation, alternative splicing defect, lead to different types of spermatogenesis alterations (e.g. decrease in primordial germ cell migration, decrease in spermatogonia proliferation), More recently defects in SCF/c-kit gene expression have also been shown in human testicular dysfunctions, Indeed, a reduction in SCF/c-kit expression has been evidenced in oligozoospermia/azoospermia associated with an increase in the germ cell apoptosis process. 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 spermatogenesis and, as a corollary, its potential involvement in spermatogenic defects.