MicroRNA. , microrna(mirna),, mirna mirna, mirna, mirna, mirna. : ; (NOA); microrna (mirna); : R698.2 : A : X(2014)
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1 34 11 Vol.34 No Nov Reproduction & Contraception doi: /j.issn X MicroRNA ( ) microrna() : ; (NOA); microrna (); : R698.2 : A : X(2014) %~ 15% 50% [2] (non-obstructive azoospermia NOA) (obstructive azoospermia OA) [3] OA (intracytoplasmic sperm injection ICSI) NOA : : ; Tel: ; caoyunxia6@126.com [1] Y 60%~70% NOA 3 : (hypo-spermato genesis) [Sertoli-cell-only (SCO) syndrome] (spermatogenesis arrest) (maturation arrest MA) [4] mrna Tnp1 Tnp2 Prm1 Prm2 mrna [56] Prm1 [7] Prm1 3' (3'UTR) Prm1 mrna 3'UTR MicroRNA () 22 RNA Lee RNA RNA 925
2 (pri-) [8] RNA Drosha-DGCR8 RNA(pre-) 60~80 nt [9] exportin5- RanGTP [10] RNA Dicer [11] RNA (RNA-induced silencing complex RISC) [12] RISC mrna [13] 30% mrna RNA 3'UTR ( ) RISC RNA RNA / RNA [14] [15-20] s s DGCR8 Drosha Dicer [15-17] 3 ; s 3'UTR [1819] 5'UTR ; s [20] [21] Yu [22] Tnp2 mrna 3'UTR mir-122 s 1 MiRNA 1.1 Yu [22] mir-122a mir-16 mir-469 mir-34 Yan [23] Yan [24] Luo [25] [26] mir ; mir-203 mir-34b-5p [27] Novotny [28] mir-17-5p E2F1(E2F transcription factor 1) ; mir-34c TGIF2 NOTCH2 [29] ; mir-18 2(heat shock factor 2 HSF2) [30] Lian MA [3132] mircurytmlnas 19 s 154 s mir-383 qrt-pcr mir-383 Lian [3132] 1(interferon regulatory factor IRF1) mir-383 mir- 383 IRF1 IFR1 IFR1 mir- 383 IFR1 mir-383 [3334] mir-383 G1/S transition cyclin D1-CDK4-p21 CDK2 G1/S prb mir- 383-pRb Park [35] mir-383
3 X (fragile X ental retardation protein FMRP) FMRP mir- 383 IFR1 mir- 383 IFR1 FMRP mir-383 s 3 : ; ; [36-38] DNA RNA [39] [4041] (cellfree cfs-) cfs- ( ) Weber 12 cfs- [40] 12 cfs- cfs- Huang RNA [39] 1.75 mg/l (<0.1 mg/l) cfs-rna 2.40~7.28 g (Microarray) Northern (Northern Blot) - (RT- PCR) RNA RNA RNA 28S rrna 18S rrna RNA ( 5S rrna trna microrna ) Wang 4 0~7 d 8 Li [42] 20% Wang ( NOA ) s(seminal plasma s sps) 19 s 7 s(mir-34c- 5p mir-122 mir-146b-5p mir-181a mir- 374b mir-509-5p mir-513a-5p) 7 sp-s ROC sps cfs-s Wu TaqMan qrt-pcr NOA sp-s [43] 3 sp-s(mir-141 mir-429 mir-7-1-3p) NOA sp- 3 sp-s(mir- 141 mir-429 mir-7-1-3p) 24 h Wu NOA sp-s [38] mir-19b let-7a sp- 4 RNA 927
4 [1] Brugh VM Lipshultz LI. Male factor infertility: evaluation and management. Med Clin North Am (2): [2] Carlsen E Giwercman A Keiding N et al. Evidence for decreasing quality of semen during past 50 years. BMJ (6854): [3] Jarvi K Lo K Fischer A et al. CUA guideline: the workup of azoospermic males. Canadian Urological Association Journal (Journal de l Association des urologues du Canada) (3): [4] McLachlan RI Rajpert-De Meyts E Hoei-Hansen CE et al. Histological evaluation of the human testis approaches to optimizing the clinical value of the assessment: mini review. Hum Reprod (1):2-16. [5] Zhao M Shirley CR Yu YE et al. Targeted disruption of the transition protein 2 gene affects sperm chromatin structure and reduces fertility in mice. Mol Cell Biol (21): [6] Mali P Kaipia A Kangasniemi M et al. Stage-specific expression of nucleoprotein mrnas during rat and mouse spermiogenesis. Reprod Fertil Dev (4): [7] Braun RE Peschon JJ Behringer RR et al. Protamine 3'- untranslated sequences regulate temporal translational control and subcellular localization of growth hormone in spermatids of transgenic mice. Genes Dev (6): [8] Cai X Hagedorn CH Cullen BR. Human micrornas are processed from capped polyadenylated transcripts that can also function as mrnas. RNA (12): [9] Han J Lee Y Yeom KH et al. The Drosha-DGCR8 complex in primary microrna processing. Genes Dev (24): [10] Yi R Qin Y Macara IG et al. Exportin-5 mediates the nuclear export of pre-micrornas and short hairpin RNAs. Genes Dev (24): [11] Lee Y Ahn C Han J et al. The nuclear RNase III Drosha initiates microrna processing. Nature (6956): [12] Gregory RI Chendrimada TP Cooch N et al. Human RISC couples microrna biogenesis and posttranscriptional gene silencing. Cell (4): [13] Zhang C. MicroRNAs: role in cardiovascular biology and disease. Clin Sci(Lond) (12): [14] Bartel DP. MicroRNAs: genomics biogenesis mechanism and function. Cell (2): [15] Babiarz JE Ruby JG Wang Y et al. Mouse ES cells express endogenous shrnas sirnas and other Microprocessorindependent Dicer-dependent small RNAs. Genes Dev (20): [16] Ruby JG Jan CH Bartel DP. Intronic microrna precursors that bypass Drosha processing. Nature (7149):83-6. [17] Cifuentes D Xue H Taylor DW et al. A novel processing pathway independent of Dicer requires Argonaute 2 catalytic activity. Science (5986): [18] Orom UA Nielsen FC Lund AH. MicroRNA-10a binds the 5'UTR of ribosomal protein mrnas and enhances their translation. Mol Cell (4): [19] Tay Y Zhang J Thomson AM et al. MicroRNAs to Nanog Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature (7216): [20] Vasudevan S Tong Y Steitz JA. Switching from repression to activation: micrornas can up-regulate translation. Science (5858): [21] 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 (3):e1738. [22] Yu Z Raabe T Hecht NB. MicroRNA Mirn122a reduces expression of the posttranscriptionally regulated germ cell transition protein 2 (Tnp2) messenger RNA (mrna) by mrna cleavage. Biol Reprod (3): [23] Yan N Lu Y Sun H et al. A microarray for microrna profiling in mouse testis tissues. Reproduction (1):73-9. [24] Yan N Lu Y Sun H et al. Microarray profiling of micrornas expressed in testis tissues of developing primates. J Assist Reprod Genet (4): [25] Luo L Ye L Liu G et al. Microarray-based approach identifies differentially expressed micrornas in porcine sexually immature and mature testes. PloS One (8):e [26] Medeiros LA Dennis LM Gill ME et al. Mir deficiency in mice results in partially penetrant embryonic lethality and germ cell defects. Proc Natl Acad Sci U S A (34): [27] Smorag L Zheng Y Nolte J et al. MicroRNA signature in various cell types of mouse spermatogenesis: evidence for stage-specifically expressed and -34b-5p mediated spermatogenesis regulation. Biol Cell (11):
5 [28] Novotny GW Sonne SB Nielsen JE et al. Translational repression of E2F1 mrna in carcinoma in situ and normal testis correlates with expression of the mir cluster. Cell Death Differ (4): [29] Bouhallier F Allioli N Lavial F et al. Role of mir-34c microrna in the late steps of spermatogenesis. RNA (4): [30] Bjork JK Sandqvist A Elsing AN et al. mir-18 a member of Oncomir-1 targets heat shock transcription factor 2 in spermatogenesis. Development (19): [31] Lian J Tian H Liu L et al. Downregulation of microrna- 383 is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation by targeting IRF1. Cell Death Disease :e94. [32] Lian J Zhang X Tian H et al. Altered microrna expression in patients with non-obstructive azoospermia. Reprod Biol Endocrinol :13. [33] Tian H Cao YX Zhang XS et al. The targeting and functions of -383 are mediated by FMRP during spermato genesis. Cell Death Dis :e617. [34] Kroh EM Parkin RK Mitchell PS et al. Analysis of circulating microrna biomarkers in plasma and serum using quantitative reverse transcription-pcr (qrt-pcr). Methods (4): [35] Park NJ Zhou H Elashoff D et al. Salivary microrna: discovery characterization and clinical utility for oral cancer detection. Clin Cancer Res (17): [36] Hanke M Hoefig K Merz H et al. A robust methodology to study urine microrna as tumor marker: microrna-126 and microrna-182 are related to urinary bladder cancer. Urol Oncol (6): [37] Li Y Kowdley KV. Method for microrna isolation from clinical serum samples. Anal Biochem (1): [38] Wu W Hu Z Qin Y et al. Seminal plasma micrornas: potential biomarkers for spermatogenesis status. Mol Hum Reprod (10): [39] Huang S Li H Ding X et al. Presence and characterization of cell-free seminal RNA in healthy individuals: implications for noninvasive disease diagnosis and gene expression studies of the male reproductive system. Clin Chem (11): [40] Weber JA Baxter DH Zhang S et al. The microrna spectrum in 12 body fluids. Clin Chem (11): Wang C Yang C Chen X et al. Altered profile of seminal plasma micrornas in the molecular diagnosis of male infertility. Clin Chem (12): [42] Li H Huang S Guo C et al. Cell-free seminal mrna and microrna exist in different forms. PloS One (4): e [43] Wu W Qin Y Li Z et al. Genome-wide microrna expression profiling in idiopathic non-obstructive azoospermia: significant up-regulation of mir-141 mir-429 and mir-7-1-3p. Hum Reprod (7): ( ) Latest Research Progress of MicroRNA and Male Infertility Xing ZHA Xiao-jing HE Yun-xia CAO (Reproductive Center of First Affiliated Hospital of Anhui Medical University Hefei ) ABSTRACT In recent decades many researches found that microrna () is abundantly expressed in testicular tissues involving in regulation of spermatogenesis. Moreover from seminal plasma is the new marker of male infertility diagnosis. In recent years increasing attention has been paid to the role of in spermatogenesis. This paper reviews the latest research progress of the status quo of male infertility posttranscriptional regulation of and its regulatory mechanisms of spermatogenesis and relationship between seminal plasma free diagnostics of male infertility. Key words: male infertility; non-obstructive azoospermia (NOA); microrna (); spermatogenesis 929
(,, ) microrna(mirna) 19~25 nt RNA, RNA mirna mirna,, ;, mirna mirna. : microrna (mirna); ; ; ; : R321.1 : A : X(2015)
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 (); ;
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