title: Integrated miRNA and mRNA expression profiling to identify mRNA targets of dysregulated miRNAs in non-obstructive azoospermia.
abstract: The aim of this study was to identify mRNA targets of dysregulated miRNAs through the integrated analysis of miRNA and mRNA expression profiling in men with normal versus impaired spermatogenesis. The expression of mRNAs and miRNAs in testicular tissues obtained from males with non-obstructive azoospermia (NOA, n = 4) or obstructive azoospermia (OA, n = 3) with normal spermatogenesis was analyzed using microarray technology. Some of the most interesting results were validated by real time PCR using samples from the same cohort. Ninety-three miRNAs and 4172 mRNAs were differentially expressed in the NOA and normozoospermic OA patients. In addition to confirming that significantly dysregulated genes and miRNAs play pivotal roles in NOA, promising correlation signatures of these miRNA/mRNA pairs were discovered in this study. The functional classification of the miRNA/mRNA pairs revealed that differentially expressed genes were most frequently associated with spermatogenesis, the cell meiosis, the cell cycle, and the development of secondary male sexual characteristics. This is the first systematic profiling of both mRNA and miRNA in testicular tissues of patients with NOA and OA. Our results indicate that the phenotypic status of NOA is characterized by the dysfunction of normal spermatogenesis when compared with OA or normozoospermic males.
authors: Department of Urology, the First Affiliated Hospital of Xiamen University, Xiamen 361003, Fujian, China.
authors: Xuan
authors: X
authors: Zhuang
authors: Translational medicine research center, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, Fujian, China.
authors: Zhiming
authors: Z
authors: Li
authors: Translational medicine research center, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, Fujian, China.
authors: Huinuan
authors: H
authors: Lin
authors: Translational medicine research center, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, Fujian, China.
authors: Long
authors: L
authors: Gu
authors: Translational medicine research center, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, Fujian, China.
authors: Qing
authors: Q
authors: Lin
authors: Xiamen City Key Laboratory of Metabolism Disease, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, Fujian, China.
authors: Zhongxian
authors: Z
authors: Lu
authors: Translational medicine research center, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, Fujian, China.
authors: Chi-Meng
authors: CM
authors: Tzeng
mesh_terms: D000328:Adult; D053713:Azoospermia / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D015536:Down-Regulation; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
references: PLoS One. 2008;3(3):e1738
references: 18320056
references: J Urol. 2002 Nov;168(5):2197-205
references: 12394759
references: Nucleic Acids Res. 2008 Jan;36(Database issue):D149-53
references: 18158296
references: Reproduction. 2009 Jun;137(6):901-11
references: 19318589
references: Nat Rev Mol Cell Biol. 2011 Apr;12(4):246-58
references: 21427766
references: Mol Cell. 2008 Sep 26;31(6):785-99
references: 18922463
references: BMJ. 2003 Sep 20;327(7416):669-72
references: 14500443
references: Biol Reprod. 2008 Feb;78(2):342-51
references: 17928628
references: Cell. 2005 Jan 14;120(1):15-20
references: 15652477
references: Genome Res. 2003 Nov;13(11):2498-504
references: 14597658
references: BMC Syst Biol. 2010;4:51
references: 20420713
references: Hum Reprod. 2013 Mar;28(3):590-8
references: 23303554
references: Reprod Biomed Online. 2007 Jun;14(6):734-45
references: 17579990
references: Int J Mol Sci. 2008 Jun;9(6):978-99
references: 19325841
references: RNA. 2006 Feb;12(2):192-7
references: 16373484
references: Fertil Steril. 2013 Apr;99(5):1249-1255.e16
references: 23312218
references: Mol Hum Reprod. 2005 Apr;11(4):295-8
references: 15734897
references: Nucleic Acids Res. 2009 Jul;37(Web Server issue):W273-6
references: 19406924
references: Nat Genet. 2007 Oct;39(10):1278-84
references: 17893677
references: Fertil Steril. 1983 Jan;39(1):5-21
references: 6336697
references: J Med Genet. 2007 Aug;44(8):498-508
references: 17496197
references: Nat Genet. 2005 May;37(5):495-500
references: 15806104
references: Nucleic Acids Res. 2009 Jan;37(Database issue):D767-72
references: 18988627
references: Nat Genet. 2012 Feb;44(2):183-6
references: 22197933
references: N Engl J Med. 1979 Feb 1;300(5):223-7
references: 759869
references: Phys Rev Lett. 2000 Jun 26;84(26 Pt 1):5924-7
references: 10991090
references: J Biol Chem. 2004 Apr 23;279(17):17905-13
references: 14960572
references: Reprod Biol Endocrinol. 2009;7:13
references: 19210773
references: RNA. 2010 Apr;16(4):720-31
references: 20150330
references: Hum Hered. 2002;53(1):8-17
references: 11901266
references: Curr Biol. 2008 Jun 24;18(12):861-7
references: 18501605
references: BMC Bioinformatics. 2009;10:295
references: 19765283
references: Cell. 2006 Sep 22;126(6):1203-17
references: 16990141
references: Int Braz J Urol. 2012 Sep-Oct;38(5):576-94
references: 23131516
references: Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):1120-5
references: 24398516
references: Endocrinology. 1971 Mar;88(3):578-88
references: 5541296
references: Biol Reprod. 2010 May;82(5):930-9
references: 20130268
references: Nat Cell Biol. 2002 Oct;4 Suppl:s41-9
references: 12479614
references: Annu Rev Med. 2009;60:167-79
references: 19630570