Skip to main content
Log in

Association of rs1057035polymorphism in microRNA biogenesis pathway gene (DICER1) with azoospermia among Iranian population

  • Research Article
  • Published:
Genes & Genomics Aims and scope Submit manuscript

Abstract

Since genes involved in microRNA biogenesis pathways have a main role in impaired spermatogenesis, in this research, we evaluated different genotypes frequency of seven single-nucleotide polymorphisms in DICER1 and DROSHA genes. Different genotypes frequency of DICER1 (rs12323635, rs1057035, rs13078 and rs3742330) and DROSHA (rs10719, rs642321 and rs2291102) were determined by sequencing method in 385 infertile men and 120 fertile controls. It was found that CC genotype (P = 0.000) and C allele (P = 0.0) of rs1057035 T > C polymorphism were associated with idiopathic male infertility (azoospermia). Gene expression study in blood and testis samples was done by real time PCR technique. Our results showed significant under expression of DICER1 gene in blood and testis tissues of azoospermic samples (P < 0.05), but we did not observed significant difference in expression ratio between infertile men with and without C allele of rs1057035 SNP (P > 0.05). The results of this study showed that among the studied variants, only one of them in DICER1 might be associated with azoospermia, but additional studies needs in different populations and ethnics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Ambros V ((2004) The functions of animal microRNAs. Nature 431:350–355

    Article  CAS  PubMed  Google Scholar 

  • Bagga S, Bracht J, Hunter S, Massirer K, Holtz J, Eachus R, Pasquinelli AE (2005) Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell 122:553–563

    Article  CAS  PubMed  Google Scholar 

  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  PubMed  Google Scholar 

  • Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Björk JK, Sandqvist A, Elsing AN, Kotaja N, Sistonen L ((2010) MiR-18, a member of Oncomir-1, targets heat shock transcription factor 2 in spermatogenesis. Development 137:3177–3184

    Article  PubMed  Google Scholar 

  • Bouhallier F, Allioli N, Lavial F, Chalmel F, Perrard MH, Durand P, Samarut J, Pain B, Rouault JP ((2010) Role of miR-34c microRNA in the late steps of spermatogenesis. RNA 16:720–731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cai X, Hagedorn CH, Cullen BR, Hagedorn Cullen (2004) Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 10:1957–1966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cho SH, Ko JJ, Kim JO, Jeon YJ, Yoo JK, Oh J, Oh D, Kim JW, Kim NK (2015) 3′-UTR polymorphisms in the miRNA machiner genes DROSHA, DICER1, RAN, and XPO5 are associated with colorectal cancer risk in a korean population. PLoS ONE 6:e 0131125

    Google Scholar 

  • Da RP, Ros M, Chalmel F, Zimmermann C, Toppari J, Nef S, Kotaja N (2011) DICER regulates the formation and maintenance of cell-cell junctions in the mouse seminiferous epithelium. PLoS ONE 6:e25241

    Article  Google Scholar 

  • Dada R, Kumar R, Shamsi MB, Kumar R, Kucheria K, Sharma RK, Gupta SK, Gupta NP (2007) Higher frequency of Yq microdeletions in sperm DNA as compared to DNA isolated from blood. Asian. J Androl 9:720–722

    CAS  Google Scholar 

  • De Kretser DM, Baker HW (1999) Infertility in men: recent advances and continuing controversies. J Clin Endocrinol Metab 84:3443–3450

    PubMed  Google Scholar 

  • Dohle GR, Colpi GM, Hargreave TB, Papp GK, Jungwirth A, Weidner W (2005) EAU guidelines on male infertility. Eur Urol 48:703–711

    Article  CAS  PubMed  Google Scholar 

  • Faller M, Guo F, Guo (2008) MicroRNA biogenesis: there’s more than one way to skin a cat. Biochim Biophys Acta 1779:663–667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fu M, Xu K, Ye J, Xu W ((2016) Association of polymorphisms of miRNA biogenesis related genes DICER and DROSHA with azoospermia. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 33:365–368

    CAS  PubMed  Google Scholar 

  • Guzick DS, Overstreet JW, Factor-Litvak P, Brazil CK, Nakajima ST, Coutifaris C, Carson SA, Cisneros P, Steinkampf MP, Hill JA et al (2001) Sperm morphology, motility, and concentration in fertile and infertile men. N Engl J Med 345:1388–1393

    Article  CAS  PubMed  Google Scholar 

  • Hayashi K, Chuva de Sousa Lopes SM, Kaneda M, Tang F, Hajkova P, Lao K, O’Carroll D, Das PP, Tarakhovsky A, Miska EA et al (2008) MicroRNA biogenesis is required for mouse primordial germ cell development and spermatogenesis. PLoS ONE 3:e1738

    Article  PubMed  PubMed Central  Google Scholar 

  • Jie L, Xiansheng Zh, Hui T, Ning L, Yong W, Chaozhao L, Xin, Li,Fei S (2009)Altered microRNA expression in patients with non-obstructive azoospermia. Reprod Biol Endocrinol 7:13

  • Jung YW, Jeon YJ, Rah H, Kim JH, Shin JE, Choi DH, Cha SH, Kim NK ((2015) Genetic variants in microRNA machinery genes are associated [corrected] with idiopathic recurrent pregnancy loss risk. PLoS ONE 10:e0118905

    Article  Google Scholar 

  • Khazamipour N, Noruzinia M, Fatehmanesh P, Keyhanee M, Pujol P (2009) MTHFR promoter hypermethylation in testicular biopsies of patients with non-obstructive azoospermia: the role of epigenetics in male infertility. Hum Reprod 24:2361–2364

    Article  CAS  PubMed  Google Scholar 

  • Kim G-J, Georg I, Scherthan H, Merkenschlager M, Guillou F, Scherer G, Barrionuevo F (2010) Dicer is required for Sertoli cell function and survival. Int J Dev Biol 54(5):867–875

  • Korhonen HM., Yadav RP, Da Ros M., Chalmel F., Zimmermann C., Toppari J., Nef S., Kotaja N (2011) DICER regulates the formation and maintenance of cell-cell junctions in the mouse seminiferous epithelium. PLoS ONE 6:e25241

    Article  Google Scholar 

  • Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Rådmark O, Kim S, Kim VN ((2003) The nuclear RNase III Drosha initiates. microRNA Process Nat 425:415–419

    CAS  Google Scholar 

  • Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, Kim VN, Kim H, Yeom L, Baek K (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23:4051–4060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433:769–773

    Article  CAS  PubMed  Google Scholar 

  • Liu D, Li L, Fu H, Li S, Li J (2012) Inactivation of Dicer1 has a severe cumulative impact on the formation of mature germ cells in mouse testes. Biochem Biophys Res Commun 422(1):114–120

  • Maatouk DM, Loveland KL, McManus MT, Moore K, Harfe BD (2008) Dicer1 is required for differentiation of the mouse male germline. Biol Reprod 79:696–703

    Article  CAS  PubMed  Google Scholar 

  • Martin-Guerrero I, Gutierrez-Camino A, Lopez-Lopez E, Bilbao-Aldaiturriaga N, Pombar-Gomez M, Ardanaz M, Garcia-Orad A (2013) Genetic variants in miRNA processing genes and pre-miRNAs are associated with the risk of chronic lymphocytic leukemia. PLoS ONE 28:e81524

    Google Scholar 

  • Musilova K, Mraz M (2014) MicroRNAs in B cell lymphomas: how a complex biology gets more complex. Leukemia 29:1004–1017

    Article  PubMed  Google Scholar 

  • Najafipour R, Rashvand Z, Alizadeh S, Aleyasin A, Moghbelinejad S (2016) Association of (rs222859) polymorphism in exon 1 of YBX2 gene with azoospermia, among the Iranian infertile male. Andrologia 48:956–960

    Article  CAS  PubMed  Google Scholar 

  • Osuch Wojcikiewicz E, Bruzgielewicz A, Niemczyk K, Sieniawska-Buccella O, Nowak A, Walczak A, Majsterek I (2015) Association of polymorphic variants of miRNA processing genes with larynx cancer risk in a polish population. Biomed Research International Epub

  • Otsuka M, Zheng M, Hayashi M, Lee JD, Yoshino O, Lin S, Han J ((2008) Impaired microRNA processing causes corpus luteum insufficiency and infertility in mice. J Clin Invest 118:1944–1954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Papaioannou MD, Pitetti JL, Ro S, Park C, Aubry F, Schaad O, Vejnar CE, Kühne F, Descombes P, Zdobnov EM et al (2009) Sertoli cell DICER1 is essential for spermatogenesis in mice. Dev Biol 326:250–259

    Article  CAS  PubMed  Google Scholar 

  • Park JE, Heo I, Tian Y, Simanshu DK, Chang H, Jee D, Patel DJ, Kim VN (2011) Dicer recognizes the 5′ end of RNA for efficient and accuratprocessing. Nature 475:201–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qin Y, Xia Y, Wu W, Han X, Lu C, Ji G, Chen D, Wang H, Song L, Wang S et al (2012) Genetic variants in microRNA biogenesis pathway genes are associated with semen quality in a Han-Chinese population. Reprod Biomed Online 24:454–61

    Article  Google Scholar 

  • Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A (2004) Identification of mammalian microRNA host genes and transcription units. Genome Res 14:1902–1910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Romero Y, Meikar O, Papaioannou MD, Conne B, Grey C, Weier M, Pralong F, De Massy B, Kaessmann H, Vassalli JD, Kotaja N, Nef S (2011) Dicer1 depletion in male germ cells leads to infertility due to cumulative meiotic and spermiogenic defects. PLoS One 6(10):e25241

  • Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C (T) method. Nat Protoc 3:1101–1108

    Article  CAS  PubMed  Google Scholar 

  • Swan SH, Elkin EP, Fenster L ((2000) The question of declining sperm density revisited: an analysis of 101 studies published 1934–1996. Environ Health Perspect 108:961–966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tian X, Zhang B, Li X, Zhai K, Xu J, Chang J, Qiao Y, Zhou Y, Huang L, Chen J (2014) Association of microRNA-related genes (DROSHA, DICER1 and GEMIN4) polymorphisms with T-cell lymphoma prognosis. Zhonghua Xue Ye Xue Za Zhi 35:408–13

    Google Scholar 

  • Totonchi M, Mohseni Meybodi A, Borjian Boroujeni P, SedighiGilani M, Almadani N, Gourabi H (2012) Clinical data for 185 infertileIranian men with Y-chromosome microdeletion. J Assist Reprod Genet 29:847–853

    Article  PubMed  PubMed Central  Google Scholar 

  • Varela MA, Amos W (2010) Heterogeneous distribution of SNPs in the human genome: microsatellites as predictors of nucleotide diversity and divergence. Genomics 95:151–159

    Article  CAS  PubMed  Google Scholar 

  • Walsh TJ, Pera RR, Turek PJ ((2009) The genetics of male infertility. Semin Reprod Med 27:124–136

    Article  PubMed  Google Scholar 

  • WHO (2010) World health Organization DoRHaR. WHO Laboratory Manual for the Examination and Processing of Human Semen. WHO Press, Geneva

    Google Scholar 

  • Yang Y, Xiao CY, Zhou-Cun A, Zhang SZ, Li X, Zhang SX (2006) DAZ1/DAZ2 cluster deletion mediated by gr/gr recombination per se may not be sufficient for spermatogenesis impairment: a study of Chinese normozoospermic men. Asian J Androl 8:183–187

    Article  CAS  PubMed  Google Scholar 

  • Yu YY, Kuang D, Yin XX (2015) Association between the DICER rs1057035 polymorphism and cancer risk: evidence from a meta-analysis of 1,2675 individuals. Asian. Pac J Cancer Prev 16:119–24

    Article  Google Scholar 

  • Yuan L, Chu H, Wang M, Gu X, Shi D, Ma L, Zhong D, Du M, Li P, Tong N et al (2010) Genetic variation in DROSHA 3′UTR regulated by hsa-miR-27b is associated with bladder cancer risk. Int J Dev Biol 54:867–875

    Article  Google Scholar 

  • Zhang H, Liu Y, Su D, Yang Y, Bai G, Tao D et al (2011) A single nucleotide polymorphism in a miR-1302 binding site in CGA increases the risk of idiopathic male infertility. Fertil Steril 96:34–39

    Article  CAS  PubMed  Google Scholar 

  • Zhou X, Ruan J, Wang G, Zhang W, Zhang RW (2007) Characterization and identification of microRNA core promoters in four model species”. PLoS Comput Biol 3:e37

  • Zimmermann C, Romero Y, Warnefors M, Bilican A., Borel C, Smith LB, Kotaja N, Kaessmann H, Nef S (2014) Germ cell-specific targeting of DICER or DGCR8 reveals a novel role for endo-siRNAs in the progression of mammalian spermatogenesis and male fertility. PLoS ONE 9(9):e107023

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We appreciate all of the participants in current study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sahar Moghbelinejad.

Ethics declarations

Conflict of interest

Moghbelinejad S, Najafipour R and Momeni A declare that they have no conflict of interest.

Ethical approval

This case-control study was approved by the Ethical Committee of the Faculty of Medical Sciences of Qazvin Medical Science University (Qazvin, Iran) and patients gave their informed written consent.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 19 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moghbelinejad, S., Najafipour, R. & Momeni, A. Association of rs1057035polymorphism in microRNA biogenesis pathway gene (DICER1) with azoospermia among Iranian population. Genes Genom 40, 17–24 (2018). https://doi.org/10.1007/s13258-017-0605-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13258-017-0605-9

Keywords

Navigation