Differential expression of microRNAs and their messengerRNA targets in men with normal spermatogenesis versus Sertoli cell-only syndrome

Abstract

To identify the profiling of testicular microRNAs (miRNAs) that are differentially expressed in men with normal spermatogenesis versus Sertoli cell-only syndrome (SCOS), to predict the miRNA target genes, and to determine the molecular networks/pathways constituted by miRNA targets. Nine obstructive azoospermic men with normal spermatogenesis and nine SCOS men were enrolled in this study. Testicular tissues from three men with normal spermatogenesis and three men with SCOS were pooled respectively for miRNA microarray analysis, and the other 12 testicular specimens were used for subsequent quantitative real-time polymerase chain reaction analysis for validation. Moreover, the predicted targets of the differentially expressed miRNAs were identified in silico and uploaded to Ingenuity Pathway Analysis for further network/pathway analysis. Three miRNAs that were upregulated (miR-136, miR-630, and miR-663) and seven miRNAs that were downregulated (miR-15b, miR-18a, miR-25, miR-30a-5p, miR-34b, miR-93, and miR-126) in SCOS specimens were identified. A total of 51 spermatogenesis-related targets were predicted in silico. Results from quantitative reverse transcription polymerase chain reaction generally correlate with microarray and computational analysis. Three significant molecular networks and five canonical pathways associated with biological functions of steroidogenesis and spermatogenesis were identified. Aberrant expression of 10 differentially expressed miRNAs might result in dysregulation of steroidogenesis and spermatogenesis that may ultimately lead to SCOS.