Issue
New insights into the expression profile of MicroRNA-34c and P53 in infertile men spermatozoa and testicular tissue
Corresponding Author(s) : S. Rahbar
Cellular and Molecular Biology,
Vol. 63 No. 8: Issue 8
Abstract
The patients were assigned to five groups based on semen analysis (n=55), including normozoospermic (N), moderate oligoasthenoteratozoospermic (MOAT), severe oligoasthenoteratozoospermic (SOAT), obstructive azoospermia (OA) and non-obstructive azoospermia (NOA). Quantitative RT-PCR was recruited to study the expression of miR-34c and tumor suppressor p53 gene. In addition, malondialdehyde (MDA) and DNA fragmentation was measured. Network analysis was performed using Pathway Studio web tool (Elsevier). Our results revealed statistically significant increased expression of miR-34c in moderate oligoasthenoteratozoospermic, non-obstructive azoospermia and an increased expression of p53 in MOAT, SOAT and NOA males. Also, the percentage of DNA fragmentation and oxidative stress was significantly higher in infertile groups (MOAT and SOAT) than other groups. These findings provide a novel molecular mechanism of gene regulation during cell-cycle and apoptosis in sperm, which gives a new regulatory insight into male infertility in terms of molecular diagnosis.
Keywords
Download Citation
Endnote/Zotero/Mendeley (RIS)BibTeX
- Rowe PJ, Comhaire FH, Hargreave TB, et al. WHO manual for the standardized investigation and diagnosis of the infertile male. Cambridge University Press, 2000.
- Bhasin S, De Kretser D, Baker H. Clinical review 64: Pathophysiology and natural history of male infertility. J Clin Endocrinol Metab. 1994; 79: 1525-29.
- Inui M, Martello G, Piccolo S. MicroRNA control of signal transduction. Nature reviews Molecular cell biology. 2010; 11: 252-63.
- 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 Dis. 2010; 1: e94.
- Yan N, Lu Y, Sun H, et al. Microarray profiling of microRNAs expressed in testis tissues of developing primates. J Assist Reprod Genet. 2009; 26: 179-86.
- He Z, Kokkinaki M, Pant D, et al. Small RNA molecules in the regulation of spermatogenesis. Reproduction. 2009; 137: 901-11.
- Wang C, Yang C, Chen X, et al. Altered profile of seminal plasma microRNAs in the molecular diagnosis of male infertility. Clin Chem. 2011; 57: 1722-31.
- Lau NC, Lim LP, Weinstein EG, et al. An Abundant Class of Tiny RNAs with Probable Regulatory Roles in Caenorhabditis elegans. Science. 2001; 294: 858-62.
- Deneberg S, Kanduri M, al e. microRNA-34b/c on chromosome 11q23 is aberrantly methylated in chronic lymphocytic leukemia. Epigenetics. 2014; 9: 910–17.
- Tscherner A, Gilchrist G, Smith N, et al. MicroRNA-34 family expression in bovine gametes and preimplantation embryos. Reprod Biol Endocrinol 2014; 12.
- Bouhallier F, Alioli N, Lavial F, et al. Role of miR-34c microRNA in the late steps of spermatogenesis. RNA. 2010; 16: 720–31.
- Hermeking H. The miR-34 family in cancer and apoptosis. Cell Death Differ. 2010; 17: 193–99.
- Corney DC, Flesken-Nikitin A, Godwin AK, et al. MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res. 2007; 67: 8433-38.
- Achari C, Winslow S, Ceder Y, et al. Expression of miR-34c induces G2/M cell cycle arrest in breast cancer cells. BMC Cancer. 2014; 14.
- He L, He X, Lim LP, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007; 447: 1130-34.
- Kato M, Paranjape T, Ullrich R, et al. The mir-34 microRNA is required for the DNA damage response in vivo in C. elegans and in vitro in human breast cancer cells. Oncogene. 2009; 28: 2419-24.
- Zenz T, Mohr J, Eldering E, et al. miR-34a as part of the resistance network in chronic lymphocytic leukemia. Blood. 2009; 113: 3801-08.
- Li M, Yu M, Liu C, et al. miR-34c works downstream of p53 leading to dairy goat male germline stem-cell (mGSCs) apoptosis. Cell Prolif. 2013; 46: 223–31.
- Yamakuchi M, Ferlito M, Lowenstein CJ. miR-34a repression of SIRT1 regulates apoptosis. PNAS 2008; 105: 13421–26.
- Bommer GT, Gerin I, Feng Y, et al. p53-Mediated Activation of miRNA34 Candidate Tumor-Suppressor Genes. Curr Biol. 2007; 17: 1298–307.
- Aziz SG-G, Pashaei-Asl F, Fardyazar Z, et al. Isolation, Characterization, Cryopreservation of Human Amniotic Stem Cells and Differentiation to Osteogenic and Adipogenic Cells. PloS one. 2016; 11: e0158281.
- Nikitin A, Egorov S, Daraselia N, et al. Pathway studio”the analysis and navigation of molecular networks. Bioinformatics. 2003; 19: 2155-57.
- Novichkova S, Egorov S, Daraselia N. MedScan, a natural language processing engine for MEDLINE abstracts. Bioinformatics. 2003; 19: 1699-706.
- Placer ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Analytical biochemistry. 1966; 16: 359-64.
- Liang H, Huang L, Cao J, et al. Regulation of mammalian gene expression by exogenous microRNAs. WIREs RNA. 2012; 3: 733-42.
- Zhang S, Yu M, Liu C, et al. MIR"34c regulates mouse embryonic stem cells differentiation into male germ"like cells through RARg. Cell Biochem Funct. 2012; 30: 623-32.
- Rokavec M, Li H, Jiang L, et al. The p53/miR-34 axis in development and disease. J Mol Cell Biol. 2014; 6: 214–30.
- Abu-Halima M, Hammadeh M, Schmitt J, et al. Altered microRNA expression profiles of human spermatozoa in patients with different spermatogenic impairments. Fertility and sterility. 2013; 99: 1249-55. e16.
- Abu-Halima M, Hammadeh M, Backes C, et al. A panel of five microRNAs as potential biomarkers for the diagnosis and assessment of male infertility. Fertil Steril. 2014.
- Abu-Halima M, Backes C, Leidinger P, et al. MicroRNA expression profiles in human testicular tissues of infertile men with different histopathologic patterns. Fertil Steril. 2014; 101.
- Mostafa T, Rashed LA, Nabil NI, et al. Seminal miRNA Relationship with Apoptotic Markers and Oxidative Stress in Infertile Men with Varicocele. BioMed Research International. 2016; 2016.
- Hayashi T, Kageyama Y, Ishizaka K, et al. Requirement of Notch 1 and its ligand jagged 2 expressions for spermatogenesis in rat and human testes. Journal of andrology. 2001; 22: 999-1011.
- Yan N, Lu Y, Sun H, et al. Microarray profiling of microRNAs expressed in testis tissues of developing primates. Journal of assisted reproduction and genetics. 2009; 26: 179-86.
- Lane DP. Cancer. p53, guardian of the genome. Nature. 1992; 358: 15-16.
- Fridman JS, Lowe SW. Control of apoptosis by p53. Oncogene. 2003; 22: 9030-40.
- Gentile V, Nicotra M, Minucci S, et al. The relationship between p53 codon 72 genetic polymorphism and sperm parameters. A study of men with varicocele. Reproductive Medicine and Biology. 2015; 14: 11-15.
- Evenson DP, Wixon R. Clinical aspects of sperm DNA fragmentation detection and male infertility. Theriogenology. 2006; 65: 979-91.
- Nasimi P, Tabandeh MR, Vahdati A, et al. Busulfan induces oxidative stress-and Bcl-2 family gene-related apoptosis in epididymal sperm and testis of adult male mice. Physiology and Pharmacology. 2015; 19: 208-15.
References
Rowe PJ, Comhaire FH, Hargreave TB, et al. WHO manual for the standardized investigation and diagnosis of the infertile male. Cambridge University Press, 2000.
Bhasin S, De Kretser D, Baker H. Clinical review 64: Pathophysiology and natural history of male infertility. J Clin Endocrinol Metab. 1994; 79: 1525-29.
Inui M, Martello G, Piccolo S. MicroRNA control of signal transduction. Nature reviews Molecular cell biology. 2010; 11: 252-63.
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 Dis. 2010; 1: e94.
Yan N, Lu Y, Sun H, et al. Microarray profiling of microRNAs expressed in testis tissues of developing primates. J Assist Reprod Genet. 2009; 26: 179-86.
He Z, Kokkinaki M, Pant D, et al. Small RNA molecules in the regulation of spermatogenesis. Reproduction. 2009; 137: 901-11.
Wang C, Yang C, Chen X, et al. Altered profile of seminal plasma microRNAs in the molecular diagnosis of male infertility. Clin Chem. 2011; 57: 1722-31.
Lau NC, Lim LP, Weinstein EG, et al. An Abundant Class of Tiny RNAs with Probable Regulatory Roles in Caenorhabditis elegans. Science. 2001; 294: 858-62.
Deneberg S, Kanduri M, al e. microRNA-34b/c on chromosome 11q23 is aberrantly methylated in chronic lymphocytic leukemia. Epigenetics. 2014; 9: 910–17.
Tscherner A, Gilchrist G, Smith N, et al. MicroRNA-34 family expression in bovine gametes and preimplantation embryos. Reprod Biol Endocrinol 2014; 12.
Bouhallier F, Alioli N, Lavial F, et al. Role of miR-34c microRNA in the late steps of spermatogenesis. RNA. 2010; 16: 720–31.
Hermeking H. The miR-34 family in cancer and apoptosis. Cell Death Differ. 2010; 17: 193–99.
Corney DC, Flesken-Nikitin A, Godwin AK, et al. MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res. 2007; 67: 8433-38.
Achari C, Winslow S, Ceder Y, et al. Expression of miR-34c induces G2/M cell cycle arrest in breast cancer cells. BMC Cancer. 2014; 14.
He L, He X, Lim LP, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007; 447: 1130-34.
Kato M, Paranjape T, Ullrich R, et al. The mir-34 microRNA is required for the DNA damage response in vivo in C. elegans and in vitro in human breast cancer cells. Oncogene. 2009; 28: 2419-24.
Zenz T, Mohr J, Eldering E, et al. miR-34a as part of the resistance network in chronic lymphocytic leukemia. Blood. 2009; 113: 3801-08.
Li M, Yu M, Liu C, et al. miR-34c works downstream of p53 leading to dairy goat male germline stem-cell (mGSCs) apoptosis. Cell Prolif. 2013; 46: 223–31.
Yamakuchi M, Ferlito M, Lowenstein CJ. miR-34a repression of SIRT1 regulates apoptosis. PNAS 2008; 105: 13421–26.
Bommer GT, Gerin I, Feng Y, et al. p53-Mediated Activation of miRNA34 Candidate Tumor-Suppressor Genes. Curr Biol. 2007; 17: 1298–307.
Aziz SG-G, Pashaei-Asl F, Fardyazar Z, et al. Isolation, Characterization, Cryopreservation of Human Amniotic Stem Cells and Differentiation to Osteogenic and Adipogenic Cells. PloS one. 2016; 11: e0158281.
Nikitin A, Egorov S, Daraselia N, et al. Pathway studio”the analysis and navigation of molecular networks. Bioinformatics. 2003; 19: 2155-57.
Novichkova S, Egorov S, Daraselia N. MedScan, a natural language processing engine for MEDLINE abstracts. Bioinformatics. 2003; 19: 1699-706.
Placer ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Analytical biochemistry. 1966; 16: 359-64.
Liang H, Huang L, Cao J, et al. Regulation of mammalian gene expression by exogenous microRNAs. WIREs RNA. 2012; 3: 733-42.
Zhang S, Yu M, Liu C, et al. MIR"34c regulates mouse embryonic stem cells differentiation into male germ"like cells through RARg. Cell Biochem Funct. 2012; 30: 623-32.
Rokavec M, Li H, Jiang L, et al. The p53/miR-34 axis in development and disease. J Mol Cell Biol. 2014; 6: 214–30.
Abu-Halima M, Hammadeh M, Schmitt J, et al. Altered microRNA expression profiles of human spermatozoa in patients with different spermatogenic impairments. Fertility and sterility. 2013; 99: 1249-55. e16.
Abu-Halima M, Hammadeh M, Backes C, et al. A panel of five microRNAs as potential biomarkers for the diagnosis and assessment of male infertility. Fertil Steril. 2014.
Abu-Halima M, Backes C, Leidinger P, et al. MicroRNA expression profiles in human testicular tissues of infertile men with different histopathologic patterns. Fertil Steril. 2014; 101.
Mostafa T, Rashed LA, Nabil NI, et al. Seminal miRNA Relationship with Apoptotic Markers and Oxidative Stress in Infertile Men with Varicocele. BioMed Research International. 2016; 2016.
Hayashi T, Kageyama Y, Ishizaka K, et al. Requirement of Notch 1 and its ligand jagged 2 expressions for spermatogenesis in rat and human testes. Journal of andrology. 2001; 22: 999-1011.
Yan N, Lu Y, Sun H, et al. Microarray profiling of microRNAs expressed in testis tissues of developing primates. Journal of assisted reproduction and genetics. 2009; 26: 179-86.
Lane DP. Cancer. p53, guardian of the genome. Nature. 1992; 358: 15-16.
Fridman JS, Lowe SW. Control of apoptosis by p53. Oncogene. 2003; 22: 9030-40.
Gentile V, Nicotra M, Minucci S, et al. The relationship between p53 codon 72 genetic polymorphism and sperm parameters. A study of men with varicocele. Reproductive Medicine and Biology. 2015; 14: 11-15.
Evenson DP, Wixon R. Clinical aspects of sperm DNA fragmentation detection and male infertility. Theriogenology. 2006; 65: 979-91.
Nasimi P, Tabandeh MR, Vahdati A, et al. Busulfan induces oxidative stress-and Bcl-2 family gene-related apoptosis in epididymal sperm and testis of adult male mice. Physiology and Pharmacology. 2015; 19: 208-15.