Impact of Human Papillomavirus (HPV) on Sperm Parameters: Role of Oxidative Stress in Semen Quality
Keywords:
Human papillomavirus, Sperm parameters, Oxidative stress, High-risk HPV, Reactive oxygen species, 8-hydroxy-2'-deoxyguanosine, MalondialdehydeAbstract
OBJECTIVE: To study the impact of HPV infection and oxidative stress on normal sperm parameters.
METHODOLOGY: This case-control study was conducted in the Department of Dermatology and Venerology at the Teaching Hospital of Hilla, Hilla City, Iraq, from March 2023 to October 2024. The study recruited 70 male patients diagnosed with HPV infection and 70 HPV-negative volunteers between the ages of 18 and 45. HPV infection was confirmed by real-time PCR for viral DNA. Sperm functional characteristics were assessed on a computer-based sperm analyzer (CASA). Oxidative stress in semen was evaluated by measuring levels of ROS using 2',7’-dichlorofluorescein diacetate (DCFH-DA) fluorescence assay, the 8-hydroxy-2'-deoxyguanosine (8-OHdG) by ELISA assay, and the malondialdehyde (MDA) following the thiobarbituric acid assay.
RESULTS: The percentages of sperm total motility, progressive motility, and normal morphology were significantly reduced among HPV patients (p < 0.001). Seminal levels of ROS, 8-OHdG, and MDA were significantly higher (p < 0.001) in HPV patients compared to the control group. Sperm characteristics were inversely correlated with levels of oxidative stress markers. The highest impact of the viral infection on sperm parameters and on ROS levels was identified in patients with high-risk HPV (HR-HPV) genotype (29 (41.4%)) compared to (41 (58.6%)) of HPV low-risk (LR-HPV), (p < 0.001).
CONCLUSION: Patients with HPV infection display elevated oxidative stress and reduced semen quality. The inverse association between oxidative stress markers in HPV patients and semen parameters indicates that oxidative stress might contribute to male reproductive dysfunction.
References
1. Pérez-Soto E, Fernández-Martínez E, Oros-Pantoja R, Medel-Flores O, Miranda-Covarrubias JC, Sánchez-Monroy V. Proinflammatory and Oxidative Stress States Induced by Human Papillomavirus and Chlamydia trachomatis Coinfection Affect Sperm Quality in Asymptomatic Infertile Men. Medicina (Kaunas). 2021; 57(9): 862. doi: 10.3390/medicina57090862.
2. Olivera C, Paira DA, Olmedo A, Olmedo JJ, Tissera AD, Molina RI et al. Impact of high-risk and low-risk human papillomavirus infections on the male genital tract: effects on semen inflammation and sperm quality. Front Cellular Infect Microbiol. 2024; 14: 1420307. doi: 10.3389/fcimb.2024.1420307.
3. Sucato A, Buttà M, Bosco L, Di Gregorio L, Perino A, Capra G. Human Papillomavirus and Male Infertility: What Do We Know? Int J Mol Sci. 2023; 24(24): 17562. doi: 10.3390/ijms242417562.
4. Piroozmand A, Mousavi Nasab SD, Erami M, Hashemi SMA, Khodabakhsh E, Ahmadi N et al. Distribution of Human Papillomavirus and Antisperm Antibody in Semen and Its Association with Semen Parameters Among Infertile Men. J Reprod Infertil. 2020; 21(3): 183-88.
5. Garolla A, Mereu S, Pizzol D, Yon DK, Rahmati M, Soysal P et al. Papillomavirus infection and male infertility: A systematic review and meta-analysis. Health Sci Rep. 2024; 7(9): e70048. doi: 10.1002/hsr2.70048.
6. Wang S, Liu L, Zhang A, Song Y, Kang J, Liu X. Association between human papillomavirus infection and sperm quality: A systematic review and a meta-analysis. Andrologia. 2021; 53(5): e14034. doi: 10.1111/and.14034. Epub 2021 Mar 5.
7. Weinberg M, Sar-Shalom Nahshon C, Feferkorn I, Bornstein J. Evaluation of human papillomavirus in semen as a risk factor for low sperm quality and poor in vitro fertilization outcomes: a systematic review and meta-analysis. Fertil Steril. 2020; 113(5): 955-69.e4. doi: 10.1016/j.fertnstert.2020.01.010.
8. Pellavio G, Todaro F, Alberizzi P, Scotti C, Gastaldi G, Lolicato M et al. HPV Infection Affects Human Sperm Functionality by Inhibition of Aquaporin-8. Cells. 2020; 9(5): 1241. doi: 10.3390/cells9051241.
9. Notari T, Buttà M, Serra N, Sucato A, Rizzo G, Capra G et al. Human papillomavirus and male infertility correlation analysis following World Health Organization 2021 guidelines. Sci Rep. 2024; 14(1): 27422. doi: 10.1038/s41598-024-79047-1.
10. Pérez-Soto E, Medel-Flores MO, Fernández-Martínez E, Oros-Pantoja R, Miranda-Covarrubias JC, Sánchez-Monroy V. High-Risk HPV with Multiple Infections Promotes CYP2E1, Lipoperoxidation and Pro-Inflammatory Cytokines in Semen of Asymptomatic Infertile Men. Antioxidants. 2022; 11(6): 1051.
11. Kaltsas A. Oxidative Stress and Male Infertility: The Protective Role of Antioxidants. Medicina (Kaunas). 2023; 59(10): 1769.
12. Luttmer R, Dijkstra MG, Snijders PJ, Hompes PG, Pronk DT, Hubeek I et al. Presence of human papillomavirus in semen in relation to semen quality. Hum Reprod. 2016; 31(2): 280-6.
13. Schillaci R, Capra G, Bellavia C, Ruvolo G, Scazzone C, Venezia R et al. Detection of oncogenic human papillomavirus genotypes on spermatozoa from male partners of infertile couples. Fertility and Sterility. 2013; 100(5): 1236-40.
14. Organization WH. WHO Laboratory Manual for the Examination and Processing of Human Semen. Geneva, Switzerland: World Health Organization Press; 2021. Available from: https://www.who.int/publications/i/item/9789240030787.
15. Benedetti S, Catalani S, De Stefani S, Primiterra M, Fraternale A, Palma F et al. A microplate-based DCFH-DA assay for the evaluation of oxidative stress in whole semen. Heliyon. 2022; 8(9): e10642.
16. Hsieh YY, Chang CC, Lin CS. Seminal malondialdehyde concentration but not glutathione peroxidase activity is negatively correlated with seminal concentration and motility. Int J Biol Sci. 2006; 2(1): 23-9.
17. Cao X, Wei R, Zhang X, Zhou J, Lou J, Cui Y. Impact of human papillomavirus infection in semen on sperm progressive motility in infertile men: a systematic review and meta-analysis. Reproductive Biology and Endocrinology. 2020; 18(1): 38.
18. Tramontano L, Sciorio R, Bellaminutti S, Esteves SC, Petignat P. Exploring the potential impact of human papillomavirus on infertility and assisted reproductive technology outcomes. Reproductive Biology. 2023; 23(2): 100753.
19. Capra G, Notari T, Buttà M, Serra N, Rizzo G, Bosco L. Human Papillomavirus (HPV) Infection and Its Impact on Male Infertility. Life (Basel). 2022; 12(11): 1919.
20. Mai Z, Yang D, Wang D, Zhang J, Zhou Q, Han B et al. A narrative review of mitochondrial dysfunction and male infertility. Translational Andrology and Urology. 2024; 13(9): 2134-45.
21. Niakan S, Faghihloo E, Mofarahe Z, Novin M, Raee P, Karimi M, et al. Evaluation of Human Papillomavirus in the Semen of Infertile Men and Its Relationship with Semen Quality. Arch Clin Infect Dis. 2023; 18(4): e139376.
22. Chenafi-Adham S, Boussetta-Charfi O, Pillet S, Bourlet T. Impact of Human Papillomavirus (HPV) on Male and Female Fertility. Pathogens. 2024; 13(12): 1076.
23. Kato Y, Shigehara K, Nakagawa T, Nakata H, Iijima M, Nakashima K et al. Human papillomavirus detected in sperm of Japanese infertile males affects reproductive parameters. Int J Infect Dis. 2021; 112: 294-9.
24. Hologlu D, Gunes S, Asci R, Henkel R, Guvenc T. Association among sperm chromatin condensation, sperm DNA fragmentation and 8-OHdG in seminal plasma and semen parameters in infertile men with oligoasthenoteratozoospermia. Andrologia. 2022; 54(1): e14268.
25. Nowicka-Bauer K, Nixon B. Molecular Changes Induced by Oxidative Stress that Impair Human Sperm Motility. Antioxidants (Basel). 2020; 9(2): 134.
26. Chianese R, Pierantoni R. Mitochondrial Reactive Oxygen Species (ROS) Production Alters Sperm Quality. Antioxidants (Basel). 2021; 10(1): 92.
27. Gholinezhad M, Aliarab A, Abbaszadeh-Goudarzi G, Yousefnia-Pasha Y, Samadaian N, Rasolpour-Roshan K et al. Nitric oxide, 8-hydroxydeoxyguanosine, and total antioxidant capacity in human seminal plasma of infertile men and their relationship with sperm parameters. Clin Exp Reprod Med. 2020; 47(1): 54-60.
28. Moretti E, Cerretani D, Noto D, Signorini C, Iacoponi F, Collodel G. Relationship Between Semen IL-6, IL-33 and Malondialdehyde Generation in Human Seminal Plasma and Spermatozoa. Reprod Sci. 2021; 28(8): 2136-43.
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