Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-26T15:30:08.376Z Has data issue: false hasContentIssue false

MicroRNA expression in infertile men: its alterations and effects

Published online by Cambridge University Press:  15 August 2019

Maryam Kiani
Affiliation:
Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, shiraz, Iran
Mohammad Salehi*
Affiliation:
Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences,Tehran, Iran Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid BeheshtiUniversity of Medical Sciences, Tehran
Asghar Mogheiseh
Affiliation:
Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, shiraz, Iran
*
Address for correspondence: Mohammad Salehi. Cellular and Molecular Biology Research Center, P.O. Box 193954717, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Tel: +98 9125118872. E-mail: [email protected]

Summary

Infertility is an important reproductive health problem, and male infertility is especially important in more than half of infertility cases. Due to the importance of genetic factors in this condition, analysis of semen alone is not enough to recognize men with idiopathic infertility. A molecular non-invasive investigation is necessary to gain valuable information. Currently, microRNAs (miRNAs) are being used as non-invasive diagnostic biomarkers. miRNAs, single-stranded non-coding RNA molecules, act as post-transcriptional gene silencing regulators either by inhibition or repression of translation. Changes in the regulation of miRNAs have been investigated in several different types of male infertility, therefore the biological role of miRNA and gene targets has been defined. The purpose of this study was to review recent research on the altered expression of miRNA in semen, sperm, and testicular biopsy samples in infertile males with different types of unexplained infertility. Changes in miRNA regulation were investigated using microarray and the miRNA levels were confirmed by real-time qRT-PCR. This review explains why creating a non-invasive diagnostic method for male infertility is necessary and how changes in miRNA expression can be used as new diagnostic biomarkers in patients with differing spermatogenic and histopathologic injury.

Type
Review Article
Copyright
© Cambridge University Press 2019 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abu-Halima, M, Hammadeh, M, Schmitt, J, Leidinger, P, Keller, A, Meese, E and Backes, C (2013) Altered microRNA expression profiles of human spermatozoa in patients with different spermatogenic impairments. Fertil Steril 99, 124955.e16.CrossRefGoogle ScholarPubMed
Baldassarre, A, Felli, C, Prantera, G and Masotti, A (2017) Circulating microRNAs and bioinformatics tools to discover novel diagnostic biomarkers of paediatric diseases. Genes 8, pii: E234.CrossRefGoogle Scholar
Barceló, M, Lluís Bassas, AM and Exosomal, SL (2018) microRNAs in seminal plasma are markers of the origin of azoospermia and can predict the presence of sperm in testicular tissue. Hum Reprod 33, 1087.CrossRefGoogle ScholarPubMed
Bartel, DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–97.CrossRefGoogle ScholarPubMed
Battista, S, Colamaio, M and Fusco, A (2013) Atlas of Genetics and Cytogenetics in Oncology and Haematology, Huret, J-L; INIST-CNRS, Italy.Google Scholar
Bouhallier, F, Allioli, N, Lavial, F, Chalmel, F, Perrard, MH, Durand, P, Samarut, J, Pain, B and Rouault, JP (2010) Role of miR-34c microRNA in the late steps of spermatogenesis. RNA 16, 720–31.CrossRefGoogle ScholarPubMed
Faruq, O and Vecchione, A (2015) microRNA: diagnostic perspective. Front Med 2, 51.CrossRefGoogle ScholarPubMed
Felekkis, K, Touvana, E, Ch, Stefanou and Deltas, C (2010) microRNAs: a newly described class of encoded molecules that play a role in health and disease. Hippokratia 14, 236–40.Google ScholarPubMed
Friedman, RC, Farh, KK, Burge, CB and Bartel, DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19, 92105.CrossRefGoogle ScholarPubMed
Guzick, DS, Overstreet, JW, Factor-Litvak, P, Brazil, CK, Nakajima, ST, Coutifaris, C, Carson, SA, Cisneros, P, Steinkampf, MP, Hill, JA, Xu, D and Vogel, DL (2001) Sperm morphology, motility, and concentration in fertile and infertile men. N Engl J Med 345, 1388–93.CrossRefGoogle ScholarPubMed
Hamada, S, Seguin, F, Bujan, L, Barthelemy, C, Mieusset, R and Lansac, J (1998) Quantification by magnetic resonance spectroscopy of metabolites in seminal plasma able to differentiate different forms of azoospermia. Hum Reprod 13, 132–5.Google Scholar
Hamam, R, Hamam, D, Alsaleh, KA, Kassem, M, Zaher, W, Alfayez, M, Aldahmash, A and Alajez, NM (2017) Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers. Cell Death Dis 7, e3045.CrossRefGoogle Scholar
Han, J, Lee, Y, Yeom, KH, Kim, YK, Jin, H and Kim, VN (2004) The Drosha–DGCR8 complex in primary microRNA processing. Genes Dev 18, 3016–27CrossRefGoogle ScholarPubMed
Hargreave, TB (2000) Genetic basis of male fertility. Br Med Bull 56, 650–71.CrossRefGoogle ScholarPubMed
He, L and Hannon, GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5, 522–31.CrossRefGoogle ScholarPubMed
Herati, A, Mielnik, A, Schlegel, P and Paduch, D (2015) MP76-20 human sperm miRNA profile in patients with normozoospermia and teratozoospermia. J Urol 193, e991.CrossRefGoogle Scholar
Huang, S, Li, H, Ding, X and Xiong, C (2009) 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 55, 1967–76.CrossRefGoogle ScholarPubMed
Khazaie, Y and Nasr Esfahani, MH (2014) MicroRNA and male infertility: a potential for diagnosis. Int J Fertil Steril 8, 113–8.Google ScholarPubMed
Kline, EE, Treat, EG, Averna, TA, Davis, MS, Smith, AY and Sillerud, LO (2006) Citrate concentrations in human seminal fluid and expressed prostatic fluid determined via 1H nuclear magnetic resonance spectroscopy outperform prostate specific antigen in prostate cancer detection. J Urol 176, 2274–9.CrossRefGoogle ScholarPubMed
Kotaja, N (2014) MicroRNAs and spermatogenesis. Fertil Steril 101, 1552–62.CrossRefGoogle ScholarPubMed
Kumar, N and Singh, AK (2015) Trends of male factor infertility, an important cause of infertility: A review of literature. Hum Reprod Sci 8, 191–6.CrossRefGoogle ScholarPubMed
Landthaler, M, Yalcin, A and Tuschl, T (2004) The human DiGeorge syndrome critical region gene 8 and its D. melanogaster homolog are required for miRNA biogenesis. Curr Biol 14, 2162–7.CrossRefGoogle ScholarPubMed
Lee, Y, Ahn, C, Han, J, Choi, H, Kim, J, Yim, J, Lee, J, Provost, P, Rådmark, O, Kim, S and Kim, VN (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425, 415–9.CrossRefGoogle ScholarPubMed
Li, Y, Zhou, X, St John, MA and Wong, DT (2004) RNA profiling of cell-free saliva using microarray technology. J Dent Res 83, 199203.CrossRefGoogle ScholarPubMed
Lian, J, Tian, H, Liu, L, Zhang, XS, Li, WQ, Deng, YM, Yao, GD, Yin, MM and Sun, F (2010) Downregulation of microRNA-383 is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation by targeting IRF1. Cell Death Dis 4, e94.CrossRefGoogle Scholar
Lian, J, Zhang, X, Tian, H, Liang, N, Wang, Y, Liang, C, Li, X and Sun, F (2009) Altered microRNA expression in patients with non-obstructive azoospermia. Reprod Biol Endocrinol 7, 13.CrossRefGoogle ScholarPubMed
Lund, E, Guttinger, S, Calado, A, Dahlberg, JE and Kutay, U (2004) Nuclear export of microRNA precursors. Science 303, 95–8.CrossRefGoogle ScholarPubMed
McLachlan, RI (2013) Approach to the patient with oligozoospermia. J Clin Endocrinol Metab. 98, 873–80.CrossRefGoogle ScholarPubMed
Moldovan, L, Batte, KE, Trgovcich, J, Wisler, J, Marsh, CB and Piper, M (2014) Methodological challenges in utilizing miRNAs as circulating biomarkers. J Cell Mol Med 18, 371–90.CrossRefGoogle ScholarPubMed
Muñoz, X, Mata, A, Bassas, L and Larriba, S (2015) Altered miRNA Signature of Developing germ-cells in infertile patients relates to the severity of spermatogenic failure and persists in spermatozoa. Sci Rep 5, 17991.CrossRefGoogle ScholarPubMed
Ni, MJ, Hu, ZH, Liu, Q, Liu, MF, Lu, MH, Zhang, JS, Zhang, L and Zhang, YL (2011) Identification and characterization of a novel non-coding RNA involved in sperm maturation. PLoS One 6, e26053.CrossRefGoogle ScholarPubMed
Okada, H, Tajima, A, Shichiri, K, Tanaka, A, Tanaka, K and Inoue, I (2008) Genome-wide expression of azoospermia testes demonstrates a specific profile and implicates ART3 in genetic susceptibility. PLoS Genet 4, e26.CrossRefGoogle ScholarPubMed
Pasquinelli, AE, Hunter, S and Bracht, J (2005) MicroRNAs: a developing story. Curr Opin Genet Dev 15, 200–5.CrossRefGoogle ScholarPubMed
Poon, LL, Leung, TN, Lau, TK and Lo, YM (2000) Presence of fetal RNA in maternal plasma. Clin Chem 46, 1832–4.Google ScholarPubMed
Quaas, A and Dokras, A (2008) Diagnosis and treatment of unexplained infertility. Rev Obstet Gynecol 1, 6976.Google ScholarPubMed
Reilly, JN, McLaughlin, EA, Stanger, SJ, Anderson, AL, Hutcheon, K, Church, K, Mihalas, BP, Tyagi, S, Holt, JE, Eamens, AL and Nixon, B (2016) Characterisation of mouse epididymosomes reveals a complex profile of microRNAs and a potential mechanism for modification of the sperm epigenome. Sci Rep 6, 31794.CrossRefGoogle Scholar
Salas-Huetos, A, Blanco, J, Vidal, F, Godo, A, Grossmann, M, Pons, MC, F-Fernández, S, Garrido, N and Anton, E (2015) Spermatozoa from patients with seminal alterations exhibit a differential micro-ribonucleic acid profile. Fertil Steril 104, 591601.CrossRefGoogle ScholarPubMed
Tiberio, P, Callari, M, Angeloni, V, Daidone, MG and Appierto, V (2015) Challenges in using circulating miRNAs as cancer biomarkers. Biomed Res Int 2015, 731479.CrossRefGoogle ScholarPubMed
Wahid, F, Shehzad, A, Khan, T and Kim, YY (2010) MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta 1803, 1231–43.CrossRefGoogle ScholarPubMed
Wang, C, Yang, C, Chen, X, Yao, B, Yang, C, Zhu, C, Li, L, Wang, J, Li, X, Shao, Y, Liu, Y, Ji, J, Zhang, J, Zen, K, Zhang, CY and Zhang, C (2011) Altered profile of seminal plasma microRNAs in the molecular diagnosis of male infertility. Clin Chem 57, 1722–31.CrossRefGoogle ScholarPubMed
Wilson, R and Doudna, JA (2013) Molecular mechanisms of RNA interference. Annu Rev Biophys 42, 217–39.CrossRefGoogle ScholarPubMed
Wosnitzer, M, Goldstein, M and Hardy, MP (2014) Review of azoospermia. Spermatogenesis 31, e28218.CrossRefGoogle Scholar
Wu, W, Qin, Y, Li, Z, Dong, J, Dai, J, Lu, C, Guo, X, Zhao, Y, Zhu, Y, Zhang, W, Hang, B, Sha, J, Shen, H, Xia, Y, Hu, Z and Wang, X (2013) 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 28, 1827–36.CrossRefGoogle ScholarPubMed
Yi, R and Fuchs, E (2011) MicroRNAs and their roles in mammalian stem cells. J Cell Sci 124, 1775–83.CrossRefGoogle ScholarPubMed
Yi, R, Qin, Y, Macara, IG and Cullen, BR (2003) Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 17, 3011–6.CrossRefGoogle ScholarPubMed
Youn, JS, Cha, SH, Park, CW, Yang, KM, Kim, JY, Koong, MK, Kang, IS, Song, IO and Han, SC (2011) Predictive value of sperm motility characteristics assessed by computer-assisted sperm analysis in intrauterine insemination with superovulation in couples with unexplained infertility. Clin Exp Reprod Med 38, 4752.CrossRefGoogle ScholarPubMed