Profiling spermatogenic failure in adult testes bearing Sox9-deficient Sertoli cells identifies genes involved in feminization, inflammation and stress

Reproductive Biology and Endocrinology

Research

Philippe Demougin¹  Michael Primig²  Frédéric Chalmel²  Aurélie Lardenois²  Gerd Scherer³  Francisco Barrionuevo⁴ 

[1] Biozentrum, University of Basel, CH-4056, Basel, Switzerland;Inserm, U625, Université de Rennes 1,IFR140, F-35042, Rennes, France;Institute of Human Genetics, University of Freiburg, D-79106, Freiburg, Germany;Institute of Human Genetics, University of Freiburg, D-79106, Freiburg, Germany;Departamento de Genética e Instituto de Biotecnología, University of Granada, Granada, Spain;

关键词: Gene Ontology;    Sertoli Cell;    Seminiferous Tubule;    Testicular Tissue;    mRNA Concentration;   

DOI  :  10.1186/1477-7827-8-154

 received in 2010-11-11, accepted in 2010-12-23,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundSox9 (Sry box containing gene 9) is a DNA-binding transcription factor involved in chondrocyte development and sex determination. The protein's absence in testicular Sertoli nurse cells has been shown to disrupt testicular function in adults but little is known at the genome-wide level about molecular events concomitant with testicular break-down.MethodsTo determine the genome-wide effect on mRNA concentrations triggered by the absence of Sox9 in Sertoli cells we analysed adult testicular tissue from wild-type versus mutant mice with high-density oligonucleotide microarrays and integrated the output of this experiment with regulatory motif predictions and protein-protein network data.ResultsWe report the genome-wide mRNA signature of adult testes lacking Sox9 in Sertoli cells before and after the onset of late spermatogenic failure as compared to fertile controls. The GeneChip data integrated with evolutionarily conserved Sox9 DNA binding motifs and regulatory network data identified genes involved in feminization, stress response and inflammation.ConclusionsOur results extend previous observations that genes required for female gonadogenesis are up-regulated in the absence of Sox9 in fetal Sertoli cells to the adult stage. Importantly, we identify gene networks involved in immunological processes and stress response which is reminiscent of a phenomenon occurring in a sub-group of infertile men. This suggests mice lacking Sox9 in their Sertoli cells to be a potentially useful model for adult human testicular failure.

【 授权许可】

Unknown   
© Lardenois et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.