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Genome-wide microRNA expression profiling in idiopathic non-obstructive azoospermia: significant up-regulation of miR-141, miR-429 and miR-7-1-3p
Article from Journal - ilmiah internasional
Human Reproduction vol. 28 no. 07 (Jul. 2013)
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STUDY QUESTION What is the profile of miRNAs in seminal plasma of patients with non-obstructive azoospermia (NOA)? SUMMARY ANSWER miR-141, miR-429 and miR-7-1-3p are significantly increased in seminal plasma of patients with NOA compared with fertile controls. WHAT IS KNOWN ALREADY There is currently an urgent need to develop a noninvasive diagnostic test for NOA. Altered microRNA (miRNA) profiles have been proposed as potential biomarkers for the diagnosis of disease states. STUDY DESIGN, SIZE, DURATION A total of 200 subjects (n = 100 for NOA, n = 100 for fertile control) were recruited to participate in this study. Recruitment took place from May 2008 to June 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS We employed a strategy consisting of initial screening by TaqMan Low Density Array then further validation with a TaqMan quantitative RT–PCR assay. Validation of the profiling results was conducted in two independent phases. In addition, the expression of the three validated seminal plasma miRNAs (sp-miRNAs) was examined in testicular tissues of patients with NOA and of fertile controls. Methylation status and functional analyses were also performed for the identified sp-miRNAs. MAIN RESULTS AND THE ROLE OF CHANCE miR-141, miR-429 and miR-7-1-3p were significantly increased in seminal plasma of patients with NOA compared with fertile controls. As sensitive and specific biomarkers, the profiling of these three identified sp-miRNAs provides a novel noninvasive, semen-based test for NOA diagnosis. The methylation status of these sp-miRNAs was inversely associated with their expression patterns. Additionally, we found that Cbl and Tgfß2 were down-regulated by miR-141, while Rb1 and Pik3r3 were down-regulated by miR-7-1-3p. LIMITATIONS, REASONS FOR CAUTION miRNA expression profile was investigated in seminal plasma samples from only a small number of NOA patients. In future investigations, a larger sample size should be adopted and the functional role of the three sp-miRNAs should be further characterized in animal models. WIDER IMPLICATIONS OF THE FINDINGS Given that sp-miRNAs show reproducible and stable expression levels, they are potentially novel noninvasive biomarkers for the diagnosis of NOA. We propose that the three sp-miRNAs described above may participate in a methylation-miRNA-gene network related to NOA development. This work provides a foundation for interpretation of miRNA changes associated with pathogenesis of NOA and extends the current understanding of human NOA pathogenesis. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the following grants: Key Project of National Natural Science Foundation of China (No. 30930079), National Basic Research Program of China (973 Program) (No. 2009CB941703, 2011CB944304), National Natural Science Foundation of China (No. 81072328 and 30901232); Science and Technology Development Fund Key Project of Nanjing Medical University (No. 2012NJMU002) and Priority Academic Program Development of Jiangsu Higher Education Institutions. The funding organizations played no role in the design and conduct of the study, in collection, management, analysis and interpretation of the data, or in the presentation, review or approval of the manuscript. There are no conflicts of interest to be declared.
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