Hum. Reprod. Advance Access published online on October 6, 2007
Human Reproduction, doi:10.1093/humrep/dem292
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Cross-platform gene expression signature of human spermatogenic failure reveals inflammatory-like response
1 Department of Andrology, University Hospital Hamburg-Eppendorf, Hamburg, Germany 2 Biozentrum, Swiss Institute of Bioinformatics, Basel, Switzerland 3 Present address: GERHM-INSERM U. 625, Groupe d'Etude de la Reproduction chez l'Homme et les Mammifères, University of Rennes 1, Rennes, France
4 Correspondence addressed. Tel: +49-40-42803-1580; Fax: +49-40-42803-1554; E-mail: c.kirchhoff{at}uke.uni-hamburg.de
BACKGROUND: The molecular basis of human testicular dysfunction is largely unknown. Global gene expression profiling of testicular biopsies might reveal an expression signature of spermatogenic failure in azoospermic men.
METHODS: Sixty-nine individual testicular biopsy samples were analysed on two microarray platforms; selected genes were validated by quantitative real-time PCR and immunohistochemistry.
RESULTS: A minimum of 188 transcripts were significantly increased on both platforms. Their levels increased with the severity of spermatogenic damage and reached maximum levels in samples with Sertoli-cell-only appearance, pointing to genes expressed in somatic testicular cells. Over-represented functional annotation terms were steroid metabolism, innate defence and immune response, focal adhesion, antigen processing and presentation and mitogen-activated protein kinase K signalling pathway. For a considerable proportion of genes included in the expression signature, individual transcript levels were in keeping with the individual mast cell numbers of the biopsies. When tested on three disparate microarray data sets, the gene expression signature was able to clearly distinguish normal from defective spermatogenesis. More than 90% of biopsy samples clustered correctly into the corresponding category, emphasizing the robustness of our data.
CONCLUSIONS: A gene expression signature of human spermatogenic failure was revealed which comprised well-studied examples of inflammation-related genes also increased in other pathologies, including autoimmune diseases.
Key words: testis/interstitium/mast cells/microarray/distance-weighted-discrimination
A.N.S. and C.F. contributed equally. Submitted on May 15, 2007; resubmitted on July 19, 2007; accepted on August 1, 2007.
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