Investigation of sperm hsa-mir-145-5p and MLH1 expressions, seminal oxidative stress and sperm DNA fragmentation in varicocele.


Journal

Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234

Informations de publication

Date de publication:
29 Apr 2024
Historique:
received: 29 01 2024
accepted: 08 04 2024
medline: 29 4 2024
pubmed: 29 4 2024
entrez: 29 4 2024
Statut: epublish

Résumé

Mechanisms by which varicocele causes infertility are not clear and few studies have reported that some miRNAs show expression alterations in men with varicocele. Recently, sperm promoter methylation of MLH1 has been shown to be higher in men diagnosed with varicocele. This study aimed to assess the potential effects of miR-145, which was determined to target MLH1 mRNA in silico on sperm quality and function in varicocele. Sperm miR-145 and MLH1 expressions of six infertile men with varicocele (Group 1), nine idiopathic infertile men (Group 2), and nine fertile men (control group) were analyzed by quantitative PCR. Sperm DNA fragmentation was evaluated by TUNEL and the levels of seminal oxidative damage and total antioxidant capacity were analyzed by ELISA. Our results have shown that sperm expression of miR-145 was decreased in Group 1 compared to Group 2 (P = 0.029). MLH1 expression was significantly higher in Group 2 than the controls (P = 0.048). Total antioxidant level and sperm DNA fragmentations of Group 1 and Group 2 were decreased (P = 0.001 and P = 0.011, respectively). Total antioxidant capacity was positively correlated with sperm concentration (ρ = 0.475, P = 0.019), total sperm count (ρ = 0.427, P = 0.037), motility (ρ = 0.716, P < 0.0001) and normal morphological forms (ρ = 0.613, P = 0.001) and negatively correlated with the seminal oxidative damage (ρ=-0.829, P = 0.042) in varicocele patients. This is the first study investigating the expressions of sperm miR-145 and MLH1 in varicocele patients. Further studies are needed to clarify the potential effect of miR-145 on male fertility.

Sections du résumé

BACKGROUND BACKGROUND
Mechanisms by which varicocele causes infertility are not clear and few studies have reported that some miRNAs show expression alterations in men with varicocele. Recently, sperm promoter methylation of MLH1 has been shown to be higher in men diagnosed with varicocele. This study aimed to assess the potential effects of miR-145, which was determined to target MLH1 mRNA in silico on sperm quality and function in varicocele.
METHODS METHODS
Sperm miR-145 and MLH1 expressions of six infertile men with varicocele (Group 1), nine idiopathic infertile men (Group 2), and nine fertile men (control group) were analyzed by quantitative PCR. Sperm DNA fragmentation was evaluated by TUNEL and the levels of seminal oxidative damage and total antioxidant capacity were analyzed by ELISA.
RESULTS RESULTS
Our results have shown that sperm expression of miR-145 was decreased in Group 1 compared to Group 2 (P = 0.029). MLH1 expression was significantly higher in Group 2 than the controls (P = 0.048). Total antioxidant level and sperm DNA fragmentations of Group 1 and Group 2 were decreased (P = 0.001 and P = 0.011, respectively). Total antioxidant capacity was positively correlated with sperm concentration (ρ = 0.475, P = 0.019), total sperm count (ρ = 0.427, P = 0.037), motility (ρ = 0.716, P < 0.0001) and normal morphological forms (ρ = 0.613, P = 0.001) and negatively correlated with the seminal oxidative damage (ρ=-0.829, P = 0.042) in varicocele patients.
CONCLUSION CONCLUSIONS
This is the first study investigating the expressions of sperm miR-145 and MLH1 in varicocele patients. Further studies are needed to clarify the potential effect of miR-145 on male fertility.

Identifiants

pubmed: 38683237
doi: 10.1007/s11033-024-09534-1
pii: 10.1007/s11033-024-09534-1
doi:

Substances chimiques

MicroRNAs 0
MIRN145 microRNA, human 0
MutL Protein Homolog 1 EC 3.6.1.3
MLH1 protein, human 0
Antioxidants 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

588

Subventions

Organisme : Türkiye Bilimsel ve Teknolojik Araştırma Kurumu
ID : 221S002

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature B.V.

Références

Alsaikhan B, Alrabeeah K, Delouya G, Zini A (2016) Epidemiology of varicocele. Asian J Androl 18(2):179–181
pubmed: 26763551 pmcid: 4770482 doi: 10.4103/1008-682X.172640
Panner Selvam MK, Baskaran S, Agarwal A, Henkel R (2021) Protein profiling in unlocking the basis of varicocele-associated infertility. Andrologia 53(1):e13645
pubmed: 32453911 doi: 10.1111/and.13645
Ou N, Song Y, Xu Y, Yang Y, Liu X (2020) Identification and verification of hub microRNAs in varicocele rats through high-throughput sequencing and bioinformatics analysis. Reprod Toxicol 98:189–199
pubmed: 33022359 doi: 10.1016/j.reprotox.2020.09.012
Roque M, Esteves SC (2018) Effect of varicocele repair on sperm DNA fragmentation: a review. Int Urol Nephrol 50(4):583–603
pubmed: 29542060 doi: 10.1007/s11255-018-1839-4
Dubin L, Amelar RD (1977) Varicocelectomy: 986 cases in a twelve-year study. Urology 10(5):446–449
pubmed: 919135 doi: 10.1016/0090-4295(77)90132-7
Abolhasani Foroughi A, Dallaki M, Hosseini SA, Ariafar A (2022) Relationship of clinical and Ultrasonographic Grading of Varicocele with Semen Analysis Profile and testicular volume. J Reprod Infertil 23(2):84–92
pubmed: 36043130 pmcid: 9363911
Pozzi E, Ramasamy R, Salonia A (2023) Initial andrological evaluation of the Infertile Male. Eur Urol Focus 9(1):51–54
pubmed: 36210297 doi: 10.1016/j.euf.2022.09.012
Santana VP, James ER, Miranda-Furtado CL, Souza MF, Pompeu CP, Esteves SC et al (2020) Differential DNA methylation pattern and sperm quality in men with varicocele. Fertil Steril
Santana VP, Miranda-Furtado CL, de Oliveira-Gennaro FG, Dos Reis RM (2017) Genetics and epigenetics of varicocele pathophysiology: an overview. J Assist Reprod Genet 34(7):839–847
pubmed: 28523408 pmcid: 5476544 doi: 10.1007/s10815-017-0931-5
Santana VP, Miranda-Furtado CL, Pedroso DCC, Eiras MC, Vasconcelos MAC, Ramos ES et al (2019) The relationship among sperm global DNA methylation, telomere length, and DNA fragmentation in varicocele: a cross-sectional study of 20 cases. Syst Biol Reprod Med 65(2):95–104
pubmed: 30601031 doi: 10.1080/19396368.2018.1557762
Gunes S, Arslan MA, Hekim GNT, Asci R (2016) The role of epigenetics in idiopathic male infertility. J Assist Reprod Genet 33(5):553–569
pubmed: 26941097 pmcid: 4870443 doi: 10.1007/s10815-016-0682-8
Conflitti AC, Cicolani G, Buonacquisto A, Pallotti F, Faja F, Bianchini S et al (2023) Sperm DNA fragmentation and sperm-borne miRNAs: molecular biomarkers of embryo development? Int J Mol Sci 24(2):1007
pubmed: 36674527 pmcid: 9864861 doi: 10.3390/ijms24021007
Ashrafzade AM, Sadighi Gilani MA, Topraggaleh TR, Khojasteh M, Sepidarkish M, Borjian Boroujeni P et al (2020) Oxidative stress-related miRNAs in spermatozoa may reveal the severity of damage in grade III varicocele. Andrologia 52(9):e13598
pubmed: 32478945 doi: 10.1111/and.13598
Ma Y, Zhou Y, Xiao Q, Zou SS, Zhu YC, Ping P et al (2021) Seminal exosomal mir-210-3p as a potential marker of sertoli cell damage in Varicocele. Andrology 9(1):451–459
pubmed: 33000559 doi: 10.1111/andr.12913
Manhart CM, Alani E (2016) Roles for mismatch repair family proteins in promoting meiotic crossing over. DNA Repair (Amst) 38:84–93
pubmed: 26686657 doi: 10.1016/j.dnarep.2015.11.024
Liu J, Lee R, Britton BM, London JA, Yang K, Hanne J et al (2019) MutL sliding clamps coordinate exonuclease-independent Escherichia coli mismatch repair. Nat Commun 10(1):5294
pubmed: 31757945 pmcid: 6876574 doi: 10.1038/s41467-019-13191-5
Gunes S, Agarwal A, Henkel R, Mahmutoglu AM, Sharma R, Esteves SC et al (2018) Association between promoter methylation of MLH1 and MSH2 and reactive oxygen species in oligozoospermic men-A pilot study. Andrologia. ;50(3)
Hekim N, Gunes S, Asci R, Henkel R, Abur U (2021) Semiquantitative promoter methylation of MLH1 and MSH2 genes and their impact on sperm DNA fragmentation and chromatin condensation in infertile men. Andrologia 53(1):e13827
pubmed: 33112435 doi: 10.1111/and.13827
World Health Organization (2021) WHO Laboratory Manual for the examination and Processing of Human Semen, 6th edn. WHO, Geneva, Switzerland. [(accessed on 3 December 2021)]. Available online https://www.who.int/publications/i/item/9789240030787
Lacerenza D, Caudullo G, Chierto E, Aneli S, Di Vella G, Barberis M et al (2022) Evaluation of the effects of different Sample Collection strategies on DNA/RNA co-analysis of forensic stains. Genes (Basel). ;13(6)
Bianchi E, Stermer A, Boekelheide K, Sigman M, Hall SJ, Reyes G et al (2018) High-quality human and rat spermatozoal RNA isolation for functional genomic studies. Andrology 6(2):374–383
pubmed: 29470852 pmcid: 6309170 doi: 10.1111/andr.12471
Sriram H, Khanka T, Kedia S, Tyagi P, Ghogale S, Deshpande N et al (2021) Improved protocol for plasma microRNA extraction and comparison of commercial kits. Biochem Med (Zagreb) 31(3):030705
pubmed: 34658646 doi: 10.11613/BM.2021.030705
Margaryan H, Dorosh A, Capkova J, Manaskova-Postlerova P, Philimonenko A, Hozak P et al (2015) Characterization and possible function of glyceraldehyde-3-phosphate dehydrogenase-spermatogenic protein GAPDHS in mammalian sperm. Reprod Biol Endocrinol 13:15
pubmed: 25888749 pmcid: 4369841 doi: 10.1186/s12958-015-0008-1
Hologlu D, Gunes S, Asci R, Henkel R, Guvenc T (2022) Association among sperm chromatin condensation, sperm DNA fragmentation and 8-OHdG in seminal plasma and semen parameters in infertile men with oligoasthenoteratozoospermia. Andrologia 54(1):e14268
pubmed: 34632608 doi: 10.1111/and.14268
Mahfouz R, Sharma R, Sharma D, Sabanegh E, Agarwal A (2009) Diagnostic value of the total antioxidant capacity (TAC) in human seminal plasma. Fertil Steril 91(3):805–811
pubmed: 18314108 doi: 10.1016/j.fertnstert.2008.01.022
Zhang L, Ding X, Nie S, Li-Ling J, Zhang Y, Zhang H et al (2015) Association of hsa-miR145 overexpression in human testicular cells with male infertility. Mol Med Rep 11(6):4365–4372
pubmed: 25633044 doi: 10.3892/mmr.2015.3273
Le Hars M, Castro-Vega LJ, Rajabi F, Tabatadze D, Romero M, Pinskaya M et al (2023) Pro-tumorigenic role of lnc-ZNF30-3 as a sponge counteracting mir-145-5p in prostate cancer. Biol Direct 18(1):38
pubmed: 37434219 pmcid: 10334624 doi: 10.1186/s13062-023-00393-7
Silva J, Tavares V, Afonso A, Garcia J, Cerqueira F, Medeiros R (2023) Plasmatic MicroRNAs and treatment outcomes of patients with metastatic castration-resistant prostate Cancer: a hospital-based Cohort Study and in Silico Analysis. Int J Mol Sci. ;24(10)
Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A et al (2007) A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129(7):1401–1414
pubmed: 17604727 pmcid: 2681231 doi: 10.1016/j.cell.2007.04.040
Lian J, Zhang X, Tian H, Liang N, Wang Y, Liang C et al (2009) Altered microRNA expression in patients with non-obstructive azoospermia. Reprod Biol Endocrinol 7:13
pubmed: 19210773 pmcid: 2647923 doi: 10.1186/1477-7827-7-13
Liu T, Cheng W, Gao Y, Wang H, Liu Z (2012) Microarray analysis of microRNA expression patterns in the semen of infertile men with semen abnormalities. Mol Med Rep 6(3):535–542
pubmed: 22735917 doi: 10.3892/mmr.2012.967
Yao C, Yuan Q, Niu M, Fu H, Zhou F, Zhang W et al (2017) Distinct expression profiles and novel targets of MicroRNAs in Human Spermatogonia, Pachytene Spermatocytes, and round spermatids between OA patients and NOA patients. Mol Ther Nucleic Acids 9:182–194
pubmed: 29246297 pmcid: 5645173 doi: 10.1016/j.omtn.2017.09.007
Razavi SM, Sabbaghian M, Jalili M, Divsalar A, Wolkenhauer O, Salehzadeh-Yazdi A (2017) Comprehensive functional enrichment analysis of male infertility. Sci Rep 7(1):15778
pubmed: 29150651 pmcid: 5693951 doi: 10.1038/s41598-017-16005-0
Babaei A, Moradi S, Hoseinkhani Z, Rezazadeh D, Dokaneheifard S, Asadpour R et al (2022) Expression of Hypoxia-Inducible Factor1-alpha in Varicocele Disease: a comprehensive systematic review. Reprod Sci 29(10):2731–2743
pubmed: 34313997 doi: 10.1007/s43032-021-00696-y
Blick C, Ramachandran A, McCormick R, Wigfield S, Cranston D, Catto J et al (2015) Identification of a hypoxia-regulated miRNA signature in bladder cancer and a role for miR-145 in hypoxia-dependent apoptosis. Br J Cancer 113(4):634–644
pubmed: 26196183 pmcid: 4647685 doi: 10.1038/bjc.2015.203
Sun N, Meng F, Xue N, Pang G, Wang Q, Ma H (2018) Inducible miR-145 expression by HIF-1a protects cardiomyocytes against apoptosis via regulating SGK1 in simulated myocardial infarction hypoxic microenvironment. Cardiol J 25(2):268–278
pubmed: 28980287
Luo DY, Yang G, Liu JJ, Yang YR, Dong Q (2011) Effects of varicocele on testosterone, apoptosis and expression of StAR mRNA in rat leydig cells. Asian J Androl 13(2):287–291
pubmed: 21076439 doi: 10.1038/aja.2010.111
Zeinali T, Mansoori B, Mohammadi A, Baradaran B (2019) Regulatory mechanisms of miR-145 expression and the importance of its function in cancer metastasis. Biomed Pharmacother 109:195–207
pubmed: 30396077 doi: 10.1016/j.biopha.2018.10.037
Gan TQ, Xie ZC, Tang RX, Zhang TT, Li DY, Li ZY et al (2017) Clinical value of mir-145-5p in NSCLC and potential molecular mechanism exploration: a retrospective study based on GEO, qRT-PCR, and TCGA data. Tumour Biol 39(3):1010428317691683
pubmed: 28347234 doi: 10.1177/1010428317691683
Chiyomaru T, Tatarano S, Kawakami K, Enokida H, Yoshino H, Nohata N et al (2011) SWAP70, actin-binding protein, function as an oncogene targeting tumor-suppressive miR-145 in prostate cancer. Prostate 71(14):1559–1567
pubmed: 21360565 doi: 10.1002/pros.21372
Finelli R, Pallotti F, Cargnelutti F, Faja F, Carlini T, Rizzo F, Lenzi A, Paoli D, Lombardo F (2021) Sperm DNA damage and cytokines in varicocele: a case-control study. Andrologia 53(5):e14023
pubmed: 33689198 doi: 10.1111/and.14023
Agarwal A, Prabakaran S, Allamaneni SS (2006) Relationship between oxidative stress, varicocele and infertility: a meta-analysis. Reprod Biomed Online 12(5):630–633
pubmed: 16790111 doi: 10.1016/S1472-6483(10)61190-X
Hamada A, Esteves SC, Agarwal A (2013) Insight into oxidative stress in varicocele-associated male infertility: part 2. Nat Rev Urol 10(1):26–37
pubmed: 23165400 doi: 10.1038/nrurol.2012.198
Abd-Elmoaty MA, Saleh R, Sharma R, Agarwal A (2010) Increased levels of oxidants and reduced antioxidants in semen of infertile men with varicocele. Fertil Steril 94(4):1531–1534
pubmed: 20117772 doi: 10.1016/j.fertnstert.2009.12.039
Allamaneni SS, Naughton CK, Sharma RK, Thomas AJ Jr., Agarwal A (2004) Increased seminal reactive oxygen species levels in patients with varicoceles correlate with varicocele grade but not with testis size. Fertil Steril 82(6):1684–1686
pubmed: 15589881 doi: 10.1016/j.fertnstert.2004.04.071
Ishikawa T, Fujioka H, Ishimura T, Takenaka A, Fujisawa M (2007) Increased testicular 8-hydroxy-2’-deoxyguanosine in patients with varicocele. BJU Int 100(4):863–866
pubmed: 17559562 doi: 10.1111/j.1464-410X.2007.07008.x
Mostafa T, Anis T, Imam H, El-Nashar AR, Osman IA (2009) Seminal reactive oxygen species-antioxidant relationship in fertile males with and without varicocele. Andrologia 41(2):125–129
pubmed: 19260850 doi: 10.1111/j.1439-0272.2008.00900.x

Auteurs

Neslihan Hekim (N)

Faculty of Medicine, Department of Medical Biology, Ondokuz Mayis University, Samsun, 55139, Turkey. neslihan.taskurt@omu.edu.tr.
Graduate Institute, Department of Molecular Medicine, Ondokuz Mayis University, Samsun, Turkey. neslihan.taskurt@omu.edu.tr.

Sezgin Gunes (S)

Faculty of Medicine, Department of Medical Biology, Ondokuz Mayis University, Samsun, 55139, Turkey.
Graduate Institute, Department of Molecular Medicine, Ondokuz Mayis University, Samsun, Turkey.

Sercan Ergun (S)

Faculty of Medicine, Department of Medical Biology, Ondokuz Mayis University, Samsun, 55139, Turkey.
Graduate Institute, Department of Molecular Medicine, Ondokuz Mayis University, Samsun, Turkey.

Elzem Nisa Barhan (EN)

Faculty of Medicine, Department of Medical Biology, Ondokuz Mayis University, Samsun, 55139, Turkey.

Ramazan Asci (R)

Graduate Institute, Department of Molecular Medicine, Ondokuz Mayis University, Samsun, Turkey.
Faculty of Medicine, Department of Urology, Ondokuz Mayis University, Samsun, Turkey.

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