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Molecular Genetics of Male Infertility: Stem Cell Factor/c-kit System

Authors

  • PAOLA GRIMALDI,

    1. PAOLA GRIMALDI, PELLEGRINO ROSSI, SUSANNA DOLCI, RAFFAELE GEREMIA, Dipartimento di Sanita′ Pubblica e Biologia Cellulare, Sezione di Anatomia, Universita′ degli Studi di Roma, Roma, Italy,
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  • PELLEGRINO ROSSI,

    1. PAOLA GRIMALDI, PELLEGRINO ROSSI, SUSANNA DOLCI, RAFFAELE GEREMIA, Dipartimento di Sanita′ Pubblica e Biologia Cellulare, Sezione di Anatomia, Universita′ degli Studi di Roma, Roma, Italy,
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  • SUSANNA DOLCI,

    1. PAOLA GRIMALDI, PELLEGRINO ROSSI, SUSANNA DOLCI, RAFFAELE GEREMIA, Dipartimento di Sanita′ Pubblica e Biologia Cellulare, Sezione di Anatomia, Universita′ degli Studi di Roma, Roma, Italy,
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  • CARLA B. RIPAMONTI,

    1. CARLA B. RIPAMONTI, Dipartimento di Biologia e Genetica per le Scienze Mediche, Universita′ di Milano, Milano, Italy
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  • RAFFAELE GEREMIA

    1. PAOLA GRIMALDI, PELLEGRINO ROSSI, SUSANNA DOLCI, RAFFAELE GEREMIA, Dipartimento di Sanita′ Pubblica e Biologia Cellulare, Sezione di Anatomia, Universita′ degli Studi di Roma, Roma, Italy,
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Paola Grimaldi Cattedra di Anatomia, Dip.to di Sanita' Pubblica e Biologia Cellulare, Universita' degli Studi di Roma `Tor Vergata', Via Montpellier, 1, 00133 Roma, Italy. E-mail: grimaldi@uniroma2.it

Abstract

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.

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