• PMID: 12322893
• Gene Name: KIT
• Condition: Idiopathic azoospermic
• Association: Associated
• Mutation: c-kit (Y721)
• Population size: 65
• Population details: 65 idiopathic azoospermic patients
• Sex: Male
• Infertility type: Male infertility
• Associated genes: c-kit
• Other associated phenotypes: Idiopathic azoospermic

Molecular genetics of male infertility: stem cell factor/c-kit system

Grimaldi P, Rossi P, Dolci S, Ripamonti CB, Geremia R.

PROBLEM: 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 OF STUDY: 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. FAU - Grimaldi, Paola AU - Grimaldi P AD - Dipartimento di Sanita' Pubblica e Biologia Cellulare, Universita' degli Studi di Roma, Italy. grimaldi@uniroma2.it FAU - Rossi, Pellegrino AU - Rossi P FAU - Dolci, Susanna AU - Dolci S FAU - Ripamonti, Carla B AU - Ripamonti CB