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

Objective: Klinefelter Syndrome (KS) is the most common sexual chromosome abnormality (47,XXY; 46,XY/47XXY) 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 in mosaic oligospermic KS patients. Design: Gene expression profiles analysis of KS mosaic oligospermic 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 3 oligopermic mosaic KS men and from 3 controls, for a total of 6 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 mosaic KS testis versus the control ones, of respectively 303 and 747 genes related to Endocrine system disorders, Lipid metabolism, Reproductive disease, cell and organ morphology, and cell death. Conclusions: Taken together these data show the presence of several de-regulated genes involved in mosaic KS testis failure. Data show the defects in sperm production and development and defects within the somatic component of the testis. This information, associated with an early diagnosis could help to unravel possible therapeutic targets for testis failure prevention and limitation. Overall design: Gene expression profile of 3 oligozoospermic mosaic KS testicular biopsies versus 3 pooled control testicular biposies form patients with normal spermatogenesis. A total of 6 experiments was carried out including biological and technical replicates.