title: Molecular genetics of male infertility: stem cell factor/c-kit system.
abstract: OBJECTIVE
  Infertility, affects about 5% of human males and genetic factors are recognized in approximately 30% of them. The mouse represents a good model to study autosomal genes that might play a role in spermatogenesis. In mice, mutations in the c-kit gene and in the gene encoding stem cell factor (SCF) cause pleiotropic defects among which sterility. A possible involvement of the SCF/c-kit system in human spermatogenesis was investigated.
  
  
  METHODS
  A group of 65 idiopathic azoospermic patients was screened for the presence of mutations in the human c-kit gene codon encoding tyrosine 721 (Y721), analogous to Y719 in the murine c-kit gene (a residue known to be essential for a normal spermatogonial proliferation). Furthermore we have used a mouse model for studying the molecular mechanisms that regulate the transcription of the endogenous SCF gene.
  
  
  RESULTS
  No mutations have been detected on codon encoding Y721 of the human c-kit gene, in our group of infertile patients.
  
  
  CONCLUSIONS
  A larger group of azoospermic patients, including preferentially patients affected by Sertoli-cell-only syndrome, should be screened in order to exclude a role of c-kit mutations in Y721 in spermatogenesis defects. In this study we also show that the murine SCF promoter is transcriptionally active and stimulated by follicle stimulating hormone (FSH), 3'-5' cyclic adenosine monophosphate (cAMP) analogs, and IBMX in primary mouse Sertoli cells, and that the cAMP effect is cell-specific, as the SCF promoter is not stimulated in other SCF-expressing cell types tested.
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D051379:Mice; D009154:Mutation; D011401:Promoter Regions, Genetic; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D012708:Sertoli Cells / Q000378:metabolism; D013091:Spermatogenesis / Q000502:physiology; D013093:Spermatogonia / Q000502:physiology; D019089:Stem Cell Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D019089:Stem Cell Factor; D000242:Cyclic AMP; D019009:Proto-Oncogene Proteins c-kit