Potential biomarkers of nonobstructive azoospermia identified in microarray gene expression analysis

微阵列基因表达分析确定非梗阻性无精子症的潜在生物标志物

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作者:Agnieszka Malcher, Natalia Rozwadowska, Tomasz Stokowy, Tomasz Kolanowski, Piotr Jedrzejczak, Wojmir Zietkowiak, Maciej Kurpisz

Objective

To identify potential biomarkers of azoospermia to determine a particular stage of spermatogenetic differentiation. Design: GeneChip Human Gene 1.0 ST microarray with validation at mRNA and protein levels. Setting: Basic research laboratory. Patient(s): Men with various types of nonobstructive azoospermia (n = 18) and with normal spermatogenesis (n = 4). Intervention(s): Obtaining 31 testicular biopsy samples. Main outcome measure(s): Gene expression analysis using the Affymetrix Human Gene 1.0 ST microarrays on 14 selected genes according to the highest fold change, verified with quantitative polymerase chain reaction and on independent set of microarray samples. Western blot and immunohistochemistry were additionally performed. Result(s): The comparative analysis of gene expression profiles in the infertile and control groups resulted in the selection of 4,946 differentially expressed genes. AKAP4, UBQLN3, CAPN11, GGN, SPACA4, SPATA3, and FAM71F1 were the most significantly down-regulated genes in infertile patients. Global analysis also led to identification of up-regulated genes-WBSCR28, ADCY10, TMEM225, SPATS1, FSCN3, GTSF1L, and GSG1-in men with late maturation arrest. Moreover, the

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