• Wei Wu, Yufeng Qin, Zheng Li, Jing Dong, Juncheng Dai, Chuncheng Lu, Xuejiang Guo, Yang Zhao, Yong Zhu, Wei Zhang, Bo Hang, Jiahao Sha, Hongbing Shen, Yankai Xia, Zhibin Hu, and Xinru Wang.
• State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
• Hum. Reprod. 2013 Jul 1; 28 (7): 1827-36.

Study QuestionWhat is the profile of miRNAs in seminal plasma of patients with non-obstructive azoospermia (NOA)?Summary AnswermiR-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 AlreadyThere 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, DurationA 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, MethodsWe 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 ChancemiR-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 Tgfβ2 were down-regulated by miR-141, while Rb1 and Pik3r3 were down-regulated by miR-7-1-3p.Limitations, Reasons For CautionmiRNA 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 FindingsGiven 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.

16 keywords...

hide…