Klinefelter Syndrome testicular gene expression profile by a whole genome microarray approach.

Objective: Klinefelter Syndrome (KS) is the most common sexual chromosome abnormality (47,XXY) and represents the first genetic cause of male infertility. The mechanisms leading to KS testis degeneration are still unclear and no therapy is so far available for affected patients. The present study is aimed to unravel information about molecules playing a key role in the disruption of the spermatogenesis. Design: Gene expression profiles analysis of KS azoospermic testis versus normal testis, could provide useful information about the molecular basis of the alteration of the spermatogenesis. Materials and Methods: Transcriptome analysis was performed carrying out gene expression profile by a whole genome microarray approach on testis biopsies obtained from 6 azoospermic non-mosaic KS men and from 3 controls, for a total of 12 experiments. T-test and False Discovery Rate were used to evaluate differentially expressed genes. Identified transcripts were analysed by Ingenuity Pathways Analysis software to disclose genes biological functions. Results: Data analysis revealed the differentially up- and down-expression, in KS testis versus the control ones, of 656 and 247 genes related to Endocrine system development and function, Lipid metabolism, Reproductive disease, Free radical scavenging, and Cell death. Conclusions: Take together these data show the presence of several genes involved in testis microenvironment deregulation leading to the spermatogenesis failure. This information, associated with an early diagnosis could help to unravel possible therapeutic targets for testis failure prevention and limitation. Gene expression profile of 6 azoospermic KS testicular biopsies versus 3 pooled control testicular biposies form patients with normal spermatogenesis. A total of 12 experiments was carried out including biological and technical replicates.