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Mol. Hum. Reprod. Advance Access originally published online on November 17, 2006
Molecular Human Reproduction 2007 13(1):33-43; doi:10.1093/molehr/gal097
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

A new paradigm for profiling testicular gene expression during normal and disturbed human spermatogenesis

C. Feig1, C. Kirchhoff1, R. Ivell2, O. Naether3, W. Schulze1 and A.-N. Spiess1,4

1Department of Andrology, University Hospital Hamburg-Eppendorf, Hamburg, Germany, 2School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia and 3Fertility Center Hamburg, Hamburg, Germany

4 To whom correspondence should be addressed at: Department of Andrology, University Hospital Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. E-mail: a.spiess{at}uke.uni-hamburg.de


  Abstract

The aim of this study was to identify gene expression patterns of the testis that correlate with the appearance of distinct stages of male germ cells. We avoided the pitfalls of mixed pathological phenotypes of the testis and circumvented the inapplicability of using the first spermatogenic wave as done previously on rodents. This was accomplished by using 28 samples showing defined and highly homogeneous pathologies selected from 578 testicular biopsies obtained from 289 men with azoospermia (two biopsies each). The molecular signature of the different developmental stages correlated with the morphological preclassification of the testicular biopsies, as shown by resampling-based hierarchical clustering using different measures of variability. By using analysis of variance (ANOVA) and extensive permutation analysis, we filtered 1181 genes that exhibit exceptional statistical significance in testicular expression and grouped subsets with transcriptional changes within the pre-meiotic (348 genes), post-meiotic (81 genes) and terminal differentiation (38 genes) phase. Several distinct molecular classes, metabolic pathways and transcription factor binding sites are involved, depending on the transcriptional profile of the gene clusters that were built using a novel clustering procedure based on not only similarity but also statistical significance.

Key words: human spermatogenesis/microarray/male infertility/Johnsen score/germ cell development


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