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35 1 Vol.35 No.1 2015 1 Jan. 2015 Reproduction & Contraception doi: 10.7669/j.issn.0253-357X.2015.01.0037 E-mail: randc_journal@163.com microrna ( 450052) microrna() 19~25 nt RNA RNA ; : microrna (); ; ; ; : R321.1 : A : 0253-357X(2015)01-0037-05 10%~15% 2009 15%~20% 50% [12] 75% [2] [3-6] microrna() (81370682 81170569) : ; Tel: +86-371-66913311; Fax: +86-371-66913635; E-mail: syp2008@vip.sina.com 1 19~25 nt RNA RNA 3' (3'- untranslated regions 3'-UTR) RNA RNA Drosha Exportin- 5 (exportin-5-dependent) [78] s RNaseIII (Dicer) [9-11] (mirisc) 3'-UTR ; 1993 Lee (C. elegans) 37

[12] lin-4 7 Reinhart 2 let-7 : RNA RNA 20 RNA RNA microrna() 20 60%~75% 3 s [13] 30% 2 [14] [3] : [4] [15-20] [51521] Dicer Gdnf Kitl Man2a2 Serpina5 Dicer s 141 s : Y X X 2005 Yu [17] mir-469 mir-34 mir-16 mir-122a mir-470 mir-201c mir-143a mir-30b mir- 27 mir-15b mir-21 mir-471 mir-465 mir-101 mir-100 mir- 466 2007 Yan [22] 14 5 2010 Luo [23] 51 78 ; let7 mir-125a mir-9 2 [5] mir-125a let-7 let-7 Fas RAS [24] let-7 mir-125a mir-9 38

LIN28 LIN28 RNA 2009 [13] 248 5 (mir-299 mir- 376a mir-381 mir-409-5p mir-67) Dicer 5 80% Dicer Dicer 2013 Wu [25] 128 [26] X mmu-mir-351 X X [1626] 4 [6] Hu ( ) [19] 61 28 (45.9%) X X 15% X Lian 3 (non-obstructive azoospermia NOA) 2 [20] NOA 154 19 RT-PCR mir-302a mir-491-3p mir- 520d-3p mir-383 NOA 14 19 X 14q32.31 19q13.42 X NOA mir- 17~92 mir-37123 NOA Yang [18] 770 5 qrt-pcr (gene ontology GO) (Kyoto Encyclopedia of genes and genomes KEGG) p35 2013 Masood 197 68 46 3 7 5 s(hsa-mir-34b* hsamir-34b hsa-mir-34c-5p hsa-mir-449a hsa-mir- 39

449b*) [29] RNA : [1] Krausz C. Male infertility: pathogenesis and clinical diagnosis. Best Pract Res Clin Endocrinal Metab 2011 25(2):271-85. [2] Okada H Tajima A Shichiri K et al. Genome-wide expression of azoospermia testes demonstrates a specific profile and implicates ART3 in genetic susceptibility. PLoS Genet 2008 4(2):e26. [3] He Z Kokkinaki M Pant D et al. Small RNA molecules in the regulation of spermatogenesis. Reproduction 2009 137 (6):901-11. [4] Li J Liu Y Dong D et al. Evolution of an X-linked primatespecific micro RNA cluster. Mol Biol Evol 2010 27(3): 671-83. [5] Hayashi K Chuva de Sousa Lopes SM Kaneda M et al. MicroRNA biogenesis is required for mouse primordial germ cell development and spermatogenesis. PLoS One 2008 3 (3):e1738. [6] Zhong X Li N Liang S et al. Identification of micrornas regulating reprogramming factor LIN28 in embryonic stem cells and cancer cells. J Biol Chem 2010 285(53):41961-71. [7] Yi R Qin Y Macara IG et al. Exportin-5 mediates the nuclear export of pre-micrornas and short hairpin RNAs. Genes Dev 2003 17(24):3011-6. [8] Lund E Guttinger S Calado A et al. Nuclear export of microrna precursors. Science 2004 303(5654):95-8. [9] Hutvágner G McLachlan J Pasquinelli AE et al. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 2001 293(5531):834-8. [10] Carmell MA Hannon GJ. RNase III enzymes and the initiation of gene silencing. Nat Struct Mol Biol 2004 11 (3):214-8. [11] Kim VN. MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 2005 6(5):376-85. [12] Lee RC Feinbaum RL Ambros V et al. The C.elegans heterochronicgene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993 75(5):843-54. [13] Lewis BP Burge CB Bartel DP. Conserved seed pairing often flanked by adenosines indicates that thousands of human genes are microrna targets. Cell 2005 120(1): 15-20. [14] Yang J Medvedev S Reddi PP et al. The DNA/RNA-binding protein MSY2 marks specific transcripts for cytoplasmic storage in mouse male germ cells. Proc Natl Acad Sci U S A 2005 102(5):1513-8. [15] Papaioannou MD Pitetti JL Ro S et al. Sertoli cell Dicer is essential for spermatogenesis in mice. Dev Biol 2009 326 (1):250-9. Ro S Park C Sanders KM et al. Cloning and expression profiling of testis-expressed micrornas. Dev Biol 2007 311(2):592-602. [17] Yu Z Raabe T Hecht NB. MicroRNA Mirn122a reduces expression of the posttranscriptionally regulated germ cell 40

transition protein 2 (Tnp2) messenger RNA () by cleavage. Biol Reprod 2005 73(3):427-33. [18] Yang Q Hua J Wang L et al. MicroRNA and pirna profiles in normal human testis detected by next generation sequencing. PLoS One 2013 8(6):e66809. [19] Hu LWua CL Guo CC et al. Identification of micrornas predominately derived from testis and epididymis in human seminal plasma. Clin Biochem 2014 47(10-11):967-72. [20] Lian J Zhang X Tian H et al. Altered microrna expression in patients with non-obstructive azoospermia. Repord Biol Endocrinol 2009 7(13):1-10. [21] Maatouk DM Loveland KL McManus MT et al. Dicer1 is required for differentiation of the mouse male germline. Biol Reprod 2008 79(4):696-703. [22] Yan N Lu Y Sun H et al. A microarray for microrna profiling in mouse testis tissues. Reproduction 2007 134 (1):73-9. [23] Luo LYe L Liu G et al. Microarray-based approach identifies differentially expressed micrornas in porcine sexually immature and mature testes. PLoS One 2010 5(8):e11744. [24] Guo X Wu Y Hartley RS. MicroRNA-125a represses cell growth by targeting HuR in breast cancer. RNA Biol 2009 6(5):575-83. [25] Wu J Zhu H Song W et al. Identification of conservative micrornas in saanen dairy goat testis through deep sequencing. Reprod Domest Anim 2014 49(1):32-40. [26] Song R Ro S Michaels JD et al. Many X-linked micrornas escape meiotic sex chromosome inactivation. Nat Genet 2009 41(4):488-93. Masood AH Christina B Petra L et al. MicroRNA expression profiles in human testicular tissues of infertile men with different histopathologic patterns. Fertil Steril 2014 101 (1):78-86. [28] Bartel DP. MicroRNAs: genomics biogenesis mechanism and function. Cell 2004 116(2):281-97. [29]Manikkam M Guerrero-Bosagna C Tracey R et al. Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures. PLoS One 2012 7(2): e31901. (2014 5 15 ) Role of microrna in spermatogenesis Nan ZHANG Qin-ling YANG Ying-pu SUN (Reproductive Medicine Center the First Affiliated Hospital of Zhengzhou University Zhenzhou 450052) ABSTRACT MicroRNA() is a class of single-stranded RNA consisting of 20 24 nucleotides and is one of the important members of non-coding RNAs. More and more evidence suggests that is closely associated with spermgenesis. In recent years by analyzing changes in different animal species the role of s that participant in protein synthesis process of spermatogenesis formation of lacuna indirect regulation of sperm motility maintaining spermtid and Sertoli cells maturation was found. With the development of sequencing and microarray technology to detect more and more spermatogenesis related s thus the sperm or testicular tissue of normal men successfully vasectomized men and different pathological types of non-obstructive azoospermia patients were also been detected. Key words: microrna (); male infertility; regulation of gene expression; meiosis; spermatogenesis 41