title: Genome-wide microRNA expression profiling in idiopathic non-obstructive azoospermia: significant up-regulation of miR-141, miR-429 and miR-7-1-3p.
abstract: OBJECTIVE
  What is the profile of miRNAs in seminal plasma of patients with non-obstructive azoospermia (NOA)?
  
  
  CONCLUSIONS
  miR-141, miR-429 and miR-7-1-3p are significantly increased in seminal plasma of patients with NOA compared with fertile controls.
  
  
  BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  RESULTS
  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 Tgfβ2 were down-regulated by miR-141, while Rb1 and Pik3r3 were down-regulated by miR-7-1-3p.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Qin
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.forename: Chuncheng
authors.initials: C
authors.lastname: Lu
authors.forename: Xuejiang
authors.initials: X
authors.lastname: Guo
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Hang
authors.forename: Jiahao
authors.initials: J
authors.lastname: Sha
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
mesh_terms: D053713:Azoospermia / Q000235:genetics*; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D008297:Male; D008745:Methylation; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D055101:Semen Analysis; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; C533895:MIRN141 microRNA, human; C546363:MIRN429 microRNA, human; C549242:MIRN7-1 microRNA, human
keywords: DNA methylation; male infertility; microRNA; non-obstructive azoospermia; seminal plasma