شنبه 2 اسفند 1404
[Archive]
دوره 33، شماره 161 - ( 9-1404 )
جلد 33 شماره 161 صفحات 283-273 |
برگشت به فهرست نسخه ها
Ethics code: IR.SBMU.RETECH.REC.1402.566
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Saberi F, Dehghan Z, Gholijani N, Mehdinejadiani S, Taheri Z, Moayedi J, et al . Transcriptomic Changes in Patients with Severely Impaired Spermatogenesis: A Systems Biology Study. J Adv Med Biomed Res 2025; 33 (161) :273-283
URL: http://journal.zums.ac.ir/article-1-7684-fa.html
URL: http://journal.zums.ac.ir/article-1-7684-fa.html
Transcriptomic Changes in Patients with Severely Impaired Spermatogenesis: A Systems Biology Study. Journal of Advances in Medical and Biomedical Research. 1404; 33 (161) :273-283
چکیده: (473 مشاهده)
Background & Objective: Male infertility is a common condition, affecting approximately 7% of men worldwide. Spermatogenesis, the production of mature sperm cells, is tightly regulated by several genes and, dysregulation of these genes can impair normal spermatogenesis. This study aimed to identify key genes involved in the regulation of spermatogenesis.
Materials & Methods: We extracted transcriptomic data from testicular samples of patients with impaired spermatogenesis and normal controls (GSE145467, 10 patients and 10 control) from the GEO database. A protein–protein interaction network (PPIN) was constructed using the STRING database and visualized with Cytoscape v3.10.1. Network clusters were identified using the MCODE plugin. In addition, an lncRNA–miRNA–gene regulatory network was constructed, and key genes were identified using Cytoscape software. Finally, Gene Ontology (GO) analysis of the key genes was performed using the DAVID and TAM 2.0 servers.
Results: CDK1, KIF11, AURKA, TEKT1, TUBB4B, CDC25C, ENKUR, CALM3, CCDC39, TYMS, PRKACB, PRKACG, FAM166C, TMEM249, GTF2A2, NRAV lncRNA, miR-1, miR-9, and miR-27b were identified as novel crucial genes in the PPIN and gene regulatory network (GRN). Functional and pathway enrichment analysis revealed that these genes are involved in gap junction communication, long-term potentiation, GnRH signaling, motor protein function, basal transcription factor activity, cell cycle regulation, inflammation, apoptosis, hormone-mediated signaling, and tumor suppressor miRNA pathways.
Conclusion: This multi-layered systems biology analysis identified key genes and pathways associated with spermatogenic failure. Further experimental validation is needed to confirm these findings and evaluate their potential as therapeutic targets.
نوع مطالعه: مقاله پژوهشی |
موضوع مقاله:
Medical Biology
دریافت: 1404/4/31 | پذیرش: 1404/9/12 | انتشار: 1404/9/21
دریافت: 1404/4/31 | پذیرش: 1404/9/12 | انتشار: 1404/9/21
فهرست منابع
1. de Kretser DM, Loveland KL, Meinhardt A, Simorangkir D, Wreford N. Spermatogenesis. Hum Reprod. 1998;13(suppl_1):1-8. [DOI:10.1093/humrep/13.suppl_1.1] [PMID]
2. Tüttelmann F, Ruckert C, Röpke A. Disorders of spermatogenesis: Perspectives for novel genetic diagnostics after 20 years of unchanged routine. Med Genet. 2018;30(1):12-20. [DOI:10.1007/s11825-018-0181-7] [PMID] [PMCID]
3. Matzuk MM, Lamb DJ. The biology of infertility: research advances and clinical challenges. Nat Med. 2008;14(11):1197-213. [DOI:10.1038/nm.f.1895] [PMID] [PMCID]
4. Linn E, Ghanem L, Bhakta H, Greer C, Avella M. Genes Regulating Spermatogenesis and Sperm Function Associated With Rare Disorders. Front Cell Dev Biol. 2021;9:634536. [DOI:10.3389/fcell.2021.634536] [PMID] [PMCID]
5. Chan SY, Wan CWT, Law TYS, Chan DYL, Fok EKL. The Sperm Small RNA Transcriptome: Implications beyond Reproductive Disorder. Int J Mol Sci. 2022;23(24):15716. [DOI:10.3390/ijms232415716] [PMID] [PMCID]
6. Krausz C, Rosta V, Swerdloff RS, Wang C. Genetics of male infertility. Emery and rimoin's principles and practice of medical genetics and genomics: Elsevier; 2022. p. 121-47. [DOI:10.1016/B978-0-12-815236-2.00010-2]
7. Hodžić A, Maver A, Zorn B, Petrovič D, Kunej T, Peterlin B. Transcriptomic signatures for human male infertility. Front Mol Biosci. 2023;10:1226829. [DOI:10.3389/fmolb.2023.1226829] [PMID] [PMCID]
8. Laiho A, Kotaja N, Gyenesei A, Sironen A. Transcriptome profiling of the murine testis during the first wave of spermatogenesis. PLoS One. 2013;8(4):e61558. [DOI:10.1371/journal.pone.0061558] [PMID] [PMCID]
9. O'Flynn O'Brien KL, Varghese AC, Agarwal A. The genetic causes of male factor infertility: a review. Fertil Steril. 2010;93(1):1-12. [DOI:10.1016/j.fertnstert.2009.10.045] [PMID]
10. Robay A, Abbasi S, Akil A, El-Bardisi H, Arafa M, Crystal RG, et al. A systematic review on the genetics of male infertility in the era of next-generation sequencing. Arab J Urol. 2018;16(1):53-64. [DOI:10.1016/j.aju.2017.12.003] [PMID] [PMCID]
11. McCubbin NI, McCallie BR, Parks JC, Schoolcraft WB, Katz-Jaffe M. Disrupted sperm mirna expression profiles revealed a fingerprint of impaired spermatogenesis in oligozoospermia males. Fertil Steril. 2017;108(3):e139. [DOI:10.1016/j.fertnstert.2017.07.420]
12. Zhou JH, Zhou QZ, Lyu XM, Zhu T, Chen ZJ, Chen MK, et al. The expression of cysteine-rich secretory protein 2 (CRISP2) and its specific regulator miR-27b in the spermatozoa of patients with asthenozoospermia. Biol Reprod. 2015;92(1):28. [DOI:10.1095/biolreprod.114.124487] [PMID]
13. Clement TM, Inselman AL, Goulding EH, Willis WD, Eddy EM. Disrupting Cyclin Dependent Kinase 1 in Spermatocytes Causes Late Meiotic Arrest and Infertility in Mice. Biol Reprod. 2015;93(6):137. [DOI:10.1095/biolreprod.115.134940] [PMID] [PMCID]
14. Gao W, Lu J, Yang Z, Li E, Cao Y, Xie L. Mitotic Functions and Characters of KIF11 in Cancers. Biomolecules. 2024;14(4):386. [DOI:10.3390/biom14040386] [PMID] [PMCID]
15. Hara-Yokoyama M, Kurihara H, Ichinose S, Matsuda H, Ichinose S, Kurosawa M, et al. KIF11 as a Potential Marker of Spermatogenesis Within Mouse Seminiferous Tubule Cross-sections. J Histochem Cytochem. 2019;67(11):813-24. [DOI:10.1369/0022155419871027] [PMID] [PMCID]
16. Zhu Z, Li C, Yang S, Tian R, Wang J, Yuan Q, et al. Dynamics of the Transcriptome during Human Spermatogenesis: Predicting the Potential Key Genes Regulating Male Gametes Generation. Sci Rep. 2016;6:19069. [DOI:10.1038/srep19069] [PMID] [PMCID]
17. Larsson M, Norrander J, Gräslund S, Brundell E, Linck R, Ståhl S, et al. The spatial and temporal expression of Tekt1, a mouse tektin C homologue, during spermatogenesis suggest that it is involved in the development of the sperm tail basal body and axoneme. Eur J Cell Biol. 2000;79(10):718-25. [DOI:10.1078/0171-9335-00097] [PMID]
18. Feng M, Wang K, Fu S, Wei H, Mu X, Li L, et al. Tubulin TUBB4B Is Involved in Spermatogonia Proliferation and Cell Cycle Processes. Genes (Basel). 2022;13(6):1082. [DOI:10.3390/genes13061082] [PMID] [PMCID]
19. Teng YN, Chung CL, Lin YM, Pan HA, Liao RW, Kuo PL. Expression of various CDC25B isoforms in human spermatozoa. Fertil Steril. 2007;88(2):379-82. [DOI:10.1016/j.fertnstert.2006.11.186] [PMID]
20. Jungnickel MK, Sutton KA, Baker MA, Cohen MG, Sanderson MJ, Florman HM. The flagellar protein Enkurin is required for mouse sperm motility and for transport through the female reproductive tract. Biol Reprod. 2018;99(4):789-97. [DOI:10.1093/biolre/ioy105] [PMID] [PMCID]
21. Slaughter GR, Means AR. Analysis of expression of multiple genes encoding calmodulin during spermatogenesis. Mol Endocrinol. 1989;3(10):1569-78. [DOI:10.1210/mend-3-10-1569] [PMID]
22. Antony D, Becker-Heck A, Zariwala MA, Schmidts M, Onoufriadis A, Forouhan M, et al. Mutations in CCDC39 and CCDC40 are the major cause of primary ciliary dyskinesia with axonemal disorganization and absent inner dynein arms. Hum Mutat. 2013;34(3):462-72. [DOI:10.1002/humu.22261] [PMID] [PMCID]
23. Eddy EM. Regulation of gene expression during spermatogenesis. Semin Cell Dev Biol. 1998;9(4):451-7. [DOI:10.1006/scdb.1998.0201] [PMID]
24. Wang YY, Sun PB, Li K, Gao T, Zheng DW, Wu FP, et al. Protein kinases regulate hyperactivated motility of human sperm. Chin Med J (Engl). 2021;134(20):2412-4. [DOI:10.1097/CM9.0000000000001551] [PMID] [PMCID]
25. The Human Protein Atlas. Human Protein Atlas: SciLifeLab / KTH / Uppsala University (Sweden); 2025. Available from: [https://www.proteinatlas.org/]
26. Pan PY, Ke CC, Wang YY, Lin YH, Ku WC, Au CF, et al. Proteomic profiling of TBC1 domain family member 21-null sperms reveals the critical roles of TEKT 1 in their tail defects. Dev Dyn. 2024;253(11):1024-35. [DOI:10.1002/dvdy.716] [PMID]
27. Huang X, Miyata H, Wang H, Mori G, Iida-Norita R, Ikawa M, et al. A CUG-initiated CATSPERθ functions in the CatSper channel assembly and serves as a checkpoint for flagellar trafficking. Proc Natl Acad Sci U S A. 2023;120(39):e2304409120. [DOI:10.1073/pnas.2304409120] [PMID] [PMCID]
28. Han SY, Zhou L, Upadhyaya A, Lee SH, Parker KL, DeJong J. TFIIAalpha/beta-like factor is encoded by a germ cell-specific gene whose expression is up-regulated with other general transcription factors during spermatogenesis in the mouse. Biol Reprod. 2001;64(2):507-17. [DOI:10.1095/biolreprod64.2.507] [PMID]
29. Li D, Li F, Meng L, Wei H, Zhang Q, Jiang F, et al. RNF216 regulates meiosis and PKA stability in the testes. Faseb J. 2021;35(4):e21460. [DOI:10.1096/fj.202002294RR] [PMID] [PMCID]
30. Ouyang J, Zhu X, Chen Y, Wei H, Chen Q, Chi X, et al. NRAV, a long noncoding RNA, modulates antiviral responses through suppression of interferon-stimulated gene transcription. Cell Host Microbe. 2014;16(5):616-26. [DOI:10.1016/j.chom.2014.10.001] [PMID] [PMCID]
31. Pointis G, Fiorini C, Defamie N, Segretain D. Gap junctional communication in the male reproductive system. Biochim Biophys Acta. 2005;1719(1-2):102-16. [DOI:10.1016/j.bbamem.2005.09.017] [PMID]
32. Samavat M, Bartol TM, Bromer C, Hubbard DD, Hanka DC, Kuwajima M, et al. Long-Term Potentiation Produces a Sustained Expansion of Synaptic Information Storage Capacity in Adult Rat Hippocampus. bioRxiv. 2024;14:574766. [DOI:10.1101/2024.01.12.574766]
33. Ni FD, Hao SL, Yang WX. Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis. Cell Death Dis. 2019;10(8):541. [DOI:10.1038/s41419-019-1782-z] [PMID] [PMCID]
34. Hirokawa N, Takemura R. Molecular motors and mechanisms of directional transport in neurons. Nat Rev Neurosci. 2005;6(3):201-14. [DOI:10.1038/nrn1624] [PMID]
35. Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009;9(3):153-66. [DOI:10.1038/nrc2602] [PMID] [PMCID]
36. Ha TY. MicroRNAs in Human Diseases: From Cancer to Cardiovascular Disease. Immune Netw. 2011;11(3):135-54. [DOI:10.4110/in.2011.11.3.135] [PMID] [PMCID]
| بازنشر اطلاعات | |
 |
این مقاله تحت شرایط Creative Commons Attribution-NonCommercial 4.0 International License قابل بازنشر است. |
