Cross-platform gene expression signature of human spermatogenic failure reveals inflammatory-like response.
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Cross-platform gene expression signature of human spermatogenic failure reveals inflammatory-like response. / Spiess, Andrej-Nikolai; Feig, Caroline; Schulze, Wolfgang; Chalmel, Frédéric; Cappallo-Obermann, Heike; Primig, Michael; Kirchhoff, Christiane.
In: HUM REPROD, Vol. 22, No. 11, 11, 2007, p. 2936-2946.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Cross-platform gene expression signature of human spermatogenic failure reveals inflammatory-like response.
AU - Spiess, Andrej-Nikolai
AU - Feig, Caroline
AU - Schulze, Wolfgang
AU - Chalmel, Frédéric
AU - Cappallo-Obermann, Heike
AU - Primig, Michael
AU - Kirchhoff, Christiane
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 22
SP - 2936
EP - 2946
JO - HUM REPROD
JF - HUM REPROD
SN - 0268-1161
IS - 11
M1 - 11
ER -