Genome-wide microRNA expression profiling in idiopathic non-obstructive azoospermia: significant up-regulation of miR-141, miR-429 and miR-7-1-3p.
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 Tgfβ2 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.
['Wu|Wei|W|', 'Qin|Yufeng|Y|', 'Li|Zheng|Z|', 'Dong|Jing|J|', 'Dai|Juncheng|J|', 'Lu|Chuncheng|C|', 'Guo|Xuejiang|X|', 'Zhao|Yang|Y|', 'Zhu|Yong|Y|', 'Zhang|Wei|W|', 'Hang|Bo|B|', 'Sha|Jiahao|J|', 'Shen|Hongbing|H|', 'Xia|Yankai|Y|', 'Hu|Zhibin|Z|', 'Wang|Xinru|X|']
D053713:Azoospermia D020869:Gene Expression Profiling D015894:Genome, Human D006801:Humans D008297:Male D008745:Methylation D035683:MicroRNAs D055101:Semen Analysis D015854:Up-Regulation
microRNA non-obstructive azoospermia seminal plasma DNA methylation male infertility