Molecular Genetics of Male Infertility: Stem Cell Factor/c-kit System
Article first published online: 19 JUN 2002
American Journal of Reproductive Immunology
Volume 48, Issue 1, pages 27–33, July 2002
How to Cite
GRIMALDI, P., ROSSI, P., DOLCI, S., RIPAMONTI, C. B. and GEREMIA, R. (2002), Molecular Genetics of Male Infertility: Stem Cell Factor/c-kit System. American Journal of Reproductive Immunology, 48: 27–33. doi: 10.1034/j.1600-0897.2002.01095.x
- Issue published online: 19 JUN 2002
- Article first published online: 19 JUN 2002
- Submitted September 11, 2001, accepted September 21, 2001
- Male infertility;
- SCF promoter;
- c-kit gene mutations;
- Sertoli cells
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.