A comparative assessment of RNF38 and P53 genes expression in the sperm samples obtained from males with normozoospermia and asthenospermia: A case-control study


Background: Infertility is considered as a common problem appears in about 10-12% of couples in their reproductive ages. Ring finger protein 38 (RNF38) gene is a ubiquitinprotein ligase that can regulate Protein 53 (P53) and affect cellular motility.

Objective: Considering the role of P53 on cellular motility and RNF38 on the regulation of P53, the present study aimed to assess the difference between RNF38 and P53 genes expression in normozoospermic and asthenospermic samples as a diagnostic biomarker in males.

Materials and Methods: The present study was conducted among 21 asthenospermics and 63 healthy individuals. First, the real-time polymerase chain reaction technique was applied to measure the expression level of the P53 and RNF38 genes extracted from sperm samples, and the glyceraldehyde-3phosphate dehydrogenase gene was selected as the reference gene.

Results: An increase and a decrease occurred in the level of P53 and RNF38 genes expressions in asthenospermic and normozoospermic samples, respectively. In addition, a significant difference was observed between increasing P53 gene expression (p < 0.001), reducing RNF38 one, and decreasing sperm motility (p < 0.001) in asthenospermic cells compared to that of normozoospermic ones.

Conclusion: Based on the results, an increase in the expression of the P53 gene and a decrease in the expression of the RNF38 gene had a significant relationship with asthenospermia in men. Therefore, it is expected that an effective step should be adopted to diagnose the asthenospermia expression pattern by using these results.

Key words: RNF38, P53, Asthenozoospermia, Motility.

[1] Sudha G, Reddy KSN. Causes of female infertility: A cross-sectional study. Int J Latest Res Sci Technol 2013; 2: 119–123.

[2] Scarneciu I, Lupu S, Scarneciu CC. Smoking as a risk factor for the development of erectile dysfunction and infertility in men: Evaluation depending on the anxiety levels of these patients. Procedia Soc Behav Sci 2014; 127: 437–442.

[3] Agarwal A, Mulgund A, Hamada A, Renee Chyatte M. A unique view on male infertility around the globe. Reprod Biol Endocrinol 2015; 13: 37.

[4] Pereira R, Sa R, Barros A, Sousa M. Major regulatory mechanisms; involved in sperm motility. Asian J Androl 2017; 19: 5–14.

[5] Alahmar AT. Role of oxidative stress in male infertility. J Hum Reprod Sci 2019; 12: 4–18.

[6] Georgiadis AP, Kishore A, Zorrilla M, Jaffe TM, Sanfilippo JS, Volk E, et al. High quality RNA in semen and sperm: Isolation, analysis and potential application in clinical testing. J Urol 2015; 193: 352– 359.

[7] Bianchi E, Boekelheide K, Sigman M, Braun JM, Eliot M, Hall SJ, et al. Spermatozoal large RNA content is associated with semen characteristics, sociodemographic and lifestyle factors. PLoS One 2019; 14: e0216584.

[8] Kadioglu K, Ortac M. The role of sperm DNA testing on male infertility. Transl Androl Urol 2017; 6 (Suppl.): S600–S603.

[9] Zedan W, Mourad MI, Abd El-Aziz SM, Salamaam NM, Shalaby AA. Cytogenetic significance of chromosome 17 aberrations and P53 gene mutations as prognostic markers in oral squamous cell carcinoma. Diagn Pathol 2015; 10: 1–9.

[10] Grelewski PG, Bar JK. The role of p53 protein and MMP-2 tumor/stromal cells expression on progressive growth of ovarian neoplasms. Cancer Invest 2013; 31: 472–479.

[11] Lee JY, Kim HJ, Yoon NA, Lee WH, Min YJ, Ko BK, et al. Tumor suppressor p53 plays a key role in induction of both tristetraprolin and let-7 in human cancer cells. Nucleic Acids Res 2013; 41: 5614–5625.

[12] Chen J. The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harb Perspect Med 2016; 6: a026104.

[13] Sheren JE, Kassenbrock K. RNF38 encodes a nuclear ubiquitin protein ligase that modifies p53. Biochem Biophys Res Commun 2013; 440: 473–478.

[14] Xiong D, Zhu Sh-Q, Wu Y-B, Jin C, Jiang J-H, Liao Y-F, et al. Ring finger protein 38 promote non-small cell lung cancer progression by endowing cell EMT phenotype. J Cancer 2018; 9: 841–850.

[15] Huang Z, Yang P, Ge H, Yang C, Cai Y, Chen Z, et al. RING finger protein 38 mediates LIM domain binding 1 degradation and regulates cell growth in colorectal cancer. Onco Targets Ther 2020; 13: 371–379.

[16] Rape M. Ubiquitylation at the crossroads of development and disease. Nat Rev Mol Cell Biol 2018; 19: 59–70.

[17] Senft D, Qi J, Ronai ZA. Ubiquitin ligases in oncogenic transformation and cancer therapy. Nat Rev Cancer 2018; 18: 69–88.

[18] Kumar N, Singh AK. Trends of male factor infertility, an important cause of infertility: A review of literature. J Hum Reprod Sci 2015; 8: 191–196.

[19] Lotti F, Maggi M. Ultrasound of the male genital tract in relation to male reproductive health. Hum Reprod Update 2015; 21: 56–83.

[20] Noori Daloii MR, Alizadeh F. [Prognostic molecular markers in hepatocellular carcinoma]. Medical Journal of Hormozgan University 2011; 15: 74–89. (in Persian)

[21] Feroz W, Sheikh MA. Exploring the multiple roles of guardian of the genome: P53. Egypt J Med Hum Genet 2020; 21: 49.

[22] Phan TTT, LinY-C, Chou YT, Wu C-W, Lin LY. Tumor suppressor p53 restrains cancer cell dissemination by modulating mitochondrial dynamics. Oncogenesis 2022; 11: 26.

[23] Panahi A, Mirza Ahmadi S, Asaadi Tehrani G. Comparison between SPATA18 and P53 gene expressions in the sperm cells obtained from normospermic and asthenospermic samples: A case-control study. Int J Fertil Steril 2022; 16: 122– 127.

[24] Marei HE, Althani A, Afifi N, Hasan A, Caceci T, Pozzoli G, et al. p53 signaling in cancer progression and therapy. Cancer Cell International 2021; 21: 703.

[25] Kung C-P, Weber JD. It’s getting complicated- A fresh look at p53-MDM2-ARF triangle in tumorigenesis and cancer therapy. Frontiers In Cell and Developmental Biology 2022; 10: 63.

[26] Ghosh S, Bhattacharjee M, Jana NK. Gene regulation by p53 in human cancer system. Asian Pac J Cancer Biol 2022; 7: 97–109.

[27] Powell E, Piwnica-Worms D, Piwnica-Worms H. Contribution of p53 to metastasis. Cancer Discov 2014; 4: 405–414.

[28] Moradi MN, Karimi J, Khodadadi I, Amiri I, Karami M, Saidijam M, et al. Evaluation of the p53 and Thioredoxin reductase in sperm from asthenozoospermic males in comparison to normozoospermic males. Free Radic Biol Med 2018; 116: 123–128.

[29] Peng R, Zhang P-F, Yang X, Wei C-Y, Huang X-Y, Cai J-B, et al. Overexpression of RNF38 facilitates TGF- β signaling by Ubiquitination and degrading AHNAK in hepatocellular carcinoma. J Exp Clin Cancer Res 2019; 38: 113.

[30] Wan J, Zhang J, Zhang J. Expression of p53 and its mechanism in prostate cancer. Oncol Let 2018; 16: 378–382.

[31] Zhang Sh, Wu M, Zhao Y, Gu R, Peng C, Liu J, et al. Correlation of MMP-9 and p53 protein expression with prognosis in metastatic spinal tumor of lung cancer. Oncol Lett 2017; 14: 5452–5456.