1- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran 2- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran , kparivar.srbiau@gmail.com 3- Department of Anatomy and Embryology, Hamadan University of Medical Sciences, Hamadan, Iran
Abstract: (553 Views)
Background: Several factors, including molecular and genetic changes, play a role in male infertility. The p53 and SIRT1 genes are among the key molecules that play a role in regulating cellular processes such as apoptosis, DNA repair, and oxidative stress. The aim of this study was to investigate the expression levels of p53 and SIRT1 genes in the sperm of infertile men compared to healthy men. Materials and methods: This case-control study used sperm samples from 15 fertile and 15 infertile men who referred to Omid Infertility Clinic in Hamedan for infertility-related tests. Some of the above sperm were used for fertilization and the other part was frozen for molecular studies. The expression levels of genes were measured using the RT-qPCR technique. After performing IVF and ICSI in vitro fertilization, the results were compared with the results of molecular studies. Results: The p53 gene expression in the sperm of infertile men was significantly increased (P ≤0.0001), while SIRT1 gene expression was significantly decreased (P ≤0.0001). In terms of the correlation between morphology, sperm count and motility in the semen sample and blastocyst rate obtained from IVF and ICSI, no significant correlation was found with P53 and SIRT1 gene expression. Conclusion: The findings showed that increased p53 expression causes sperm apoptosis and decreased SIRT1 expression exacerbates oxidative stress; both of which can be used as key markers in the evaluation of male fertility.
1. Khawar MB, Sohail AM, Li W. SIRT1: A key player in male reproduction. Life 2022;12:318. [DOI:10.3390/life12020318]
2. Tatone C, Di Emidio G, Barbonetti A, Carta G, Luciano AM, Falone S, et al. Sirtuins in gamete biology and reproductive physiology: emerging roles and therapeutic potential in female and male infertility. Hum Reprod Update 2018;24:267-89. [DOI:10.1093/humupd/dmy003]
3. Bell EL, Nagamori I, Williams EO, Del Rosario AM, Bryson BD, Watson N, et al. SirT1 is required in the male germ cell for differentiation and fecundity in mice. Development 2014;141:3495-504. [DOI:10.1242/dev.110627]
4. Alam F, Syed H, Amjad S, Baig M, Khan TA, Rehman R. Interplay between oxidative stress, SIRT1, reproductive and metabolic functions. Curr Res Physiol 2021;4:119-24. [DOI:10.1016/j.crphys.2021.03.002]
5. Park S-A, Joo N-R, Park J-H, Oh S-M. Role of the SIRT1/p53 regulatory axis in oxidative stress‑mediated granulosa cell apoptosis. Mol Med Rep 2021;23:20. [DOI:10.3892/mmr.2020.11658]
6. Li J, Huang X, Luo L, Sun J, Guo Q, Yang X, et al. The role of p53 in male infertility. Front Endocrinol 2024;15:1457985. [DOI:10.3389/fendo.2024.1457985]
8. Xu X, Wang Z, Lv L, Liu C, Wang L, Sun Y-n, et al. Molecular regulation of DNA damage and repair in female infertility: a systematic review. Reprod Biol Endocrinol 2024;22:103. [DOI:10.1186/s12958-024-01273-z]
9. Raimondo S, Gentile T, Gentile M, Morelli A, Donnarumma F, Cuomo F, et al. p53 protein evaluation on spermatozoa DNA in fertile and infertile males. J Hum Reprod Sci 2019;12:114-21. [DOI:10.4103/jhrs.JHRS_170_18]
10. Govindhasamy R, Govindhasamy P, Vanga R, Burute P. Role of TP53 gene polymorphism in male infertility. International Journal of Infertility & Fetal Medicine. 2021;12(2):44-8. [DOI:10.5005/jp-journals-10016-1218]
11. Raimondo S, Gentile T, Cuomo F, De Filippo S, Aprea GE, Guida J. Quantitative evaluation of p53 as a new indicator of DNA damage in human spermatozoa. J Hum Reprod Sci 2014;7:212-7. [DOI:10.4103/0974-1208.142490]
12. Zhang X, Xia Q, Wei R, Song H, Mi J, Lin Z, et al. Melatonin protects spermatogonia from the stress of chemotherapy and oxidation via eliminating reactive oxidative species. Free Radic Biol Med 2019;137:74-86. [DOI:10.1016/j.freeradbiomed.2019.04.009]
13. Mashayekhi F, Hadiyan S. A single‐nucleotide polymorphism in TP53 may be a genetic risk factor for Iranian patients with idiopathic male infertility. Andrologia 2012;44:560-4. [DOI:10.1111/j.1439-0272.2011.01227.x]
14. Loganathan C, Kannan A, Panneerselvam A, Mariajoseph-Antony LF, Kumar SA, Anbarasu K, et al. The possible role of sirtuins in male reproduction. Mol Cell Biochem 2021;476:2857-67. [DOI:10.1007/s11010-021-04116-2]
15. Iniesta‐Cuerda M, Havránková J, Řimnáčová H, García‐Álvarez O, Nevoral J. Male SIRT1 insufficiency leads to sperm with decreased ability to hyperactivate and fertilize. Reprod Domest Anim 2022;57:72-7. [DOI:10.1111/rda.14172]
16. Wahab F, Rodriguez Polo I, Behr R. SIRT1 expression and regulation in the primate testis. Int J Mol Sci 2021;22:3207. [DOI:10.3390/ijms22063207]
17. Mao B-P, Li L, Yan M, Ge R, Lian Q, Cheng CY. Regulation of BTB Dynamics in Spermatogenesis-Insights From the Adjudin Model. Toxicol Sci 2019;172:75-88. [DOI:10.1093/toxsci/kfz180]
18. Pańczyszyn A, Boniewska-Bernacka E, Wertel I, Sadakierska-Chudy A, Goc A. Telomeres and SIRT1 as Biomarkers of Gamete Oxidative Stress, Fertility, and Potential IVF Outcome. Int J Mol Sci 2024;25:8652. [DOI:10.3390/ijms25168652]
19. Ye F, Wu L, Li H, Peng X, Xu Y, Li W, et al. SIRT1/PGC-1α is involved in arsenic-induced male reproductive damage through mitochondrial dysfunction, which is blocked by the antioxidative effect of zinc. Environ Pollut 2023;320:121084. [DOI:10.1016/j.envpol.2023.121084]
Ghodrati F, Parivar K, Amiri I, Hayati Roodbari N. Study of p53 and sirtuin1 gene expression levels in sperm of infertile men compared to healthy men. MEDICAL SCIENCES 2026; 36 (1) :23-33 URL: http://tmuj.iautmu.ac.ir/article-1-2383-en.html