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V. Gatta, F. Raicu, A. Scioletti, A. Ferlin, G. Palka, C. Foresta, L. Stuppia. Gene expression profiling of normal and pathological testis by microarray analysis. In EUROPEAN HUMAN GENETICS CONFERENCE, Barcelona SPAIN. 2008.

Abstract: Microdeletions of the AZFa, AZFb and AZFc loci on Yq are detected in about 10% of infertile males. Despite the large amount of data collected in the last years, the biological mechanisms leading to the disruption of spermatogenesis in Yq deleted patients are still largely unknown. In this study we analyzed by microarray technology the testis expression profiles of patients with idiopathic infertility, patients carries of AZFc deletion and controls (patients with obstructive azoospermia), in order to obtain useful information about the specific genes involved in each different pathological condition. Using the hierarchical clustering average method in 27 microarray experiments we identified in AZFc deleted patients two main gene clusters showing different expression patterns as compared to normal controls and patients with idiopathic infertility. Analysis of these gene clusters using IPA software revealed an interesting down-regulated gene network directly related with spermatogenesis, with the most significant network centred around YBX2 gene (Y box binding protein 2), involved in RNA storage during gametogenesis. This alteration is responsible for the downregulation of the protammine1 and 2 genes evidenced in the same nethwork analysis. In the expression profiles comparative analysis between controls and AZFc deleted patients we also observed an interesting downregulation of the CREM pathway, which is a master controller gene for spermatogenesis. This suggests that impairment of RNA storage and dysregulation of the CREM pathway could represent two of the biological mechanisms underlying spermatogenesis failure in patients with Yq microdeletion.



Keywords: human transcriptome, testis pathology

Posted by Florina Raicu

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