The effect of covid-19 on male fertility
Authors:
Silvie Ostřížková 1; Renata Zlotkowska 1,2
Authors place of work:
Ústav epidemiologie a ochrany veřejného zdraví, Ostravská univerzita, Ostrava, Česká republika
1; Centrum pracovního lékařství Malopolského vojvodství v Krakově, Krakov, Polsko
1, 2
Published in the journal:
Ces Urol 2022; 26(4): 224-231
Category:
Review article
Summary
Covid-19 disease has spread rapidly across continents since 2019, causing a pandemic. A higher prevalence of the disease has been observed in males, partly due to higher expression of angiotensin- converting enzyme 2 (ACE2), which, together with transmembrane serine protease 2 (TMPRSS2), plays an important role in viral entry into the cell. Both ACE2 and TMPRSS2 are expressed on the surface of many human tissues, including tissues of the male and female reproductive system. For this reason, the effect of SARS-CoV-2 on male fertility is still under investigation. Current studies have focused on histopathological changes in post mortem testicular samples from covid-19 positive patients, but also on immune responses induced by SARS-CoV-2. Cytokine storm caused by cell pyroptosis and oxidative stress may have a negative impact. As most viruses, including SARSCoV- 2, are able to break the bloodbrain barrier, the hypothalamic-pituitary-gonadal axis, essential for endocrine regulation of spermatogenesis, may also be affected. Patients with covid-19 disease show higher levels of luteinizing hormone and prolactin and lower levels of testosterone due to Leydig cell damage. Sperm analysis showed a deterioration of total sperm motility and a decrease in sperm concentration in the ejaculate. However, the effect on spermiogram parameters appears to be temporary.
Major statement: Although covid-19 is often seen as a respiratory disease, it is capable of affecting any organ system, including the reproductive system. A higher prevalence has been observed in men, in whom SARS‑CoV- 2 infection may directly or indirectly affect physiological processes related to fertility, including ongoing spermatogenesis, by a number of mechanisms.
Keywords:
COVID-19 – coronavirus – ACE2 – male fertility.
Zdroje
1. Guo YR, Cao QD, Hong ZS, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. Mil Med Res. 2020; 7(1): 11.
2. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798): 270–273.
3. Salian VS, Wright JA, Vedell PT, et al. COVID-19 Transmission, Current Treatment, and Future Therapeutic Strategies. Molecular Pharmaceutics. 2021; 18(3): 754–771.
4. Collins AB, Zhao L, Zhu Z, et al. Impact of COVID-19 on Male Fertility. Urology. 2022; 164: 33–39.
5. Gonzalez DC, Khodamoradi K, Pai R, et al. A Systematic Review on the Investigation of SARS‑CoV-2 in Semen. Res Rep Urol. 2020; 12: 615–621.
6. Haque A, Pant AB. Mitigating Covid-19 in the face of emerging virus variants, breakthrough infections and vaccine hesitancy. Journal of Autoimmunity. 2022; 127: 102792.
7. Alimohamadi Y, Sepandi M, Taghdir M, Hosamirudsari H. Determine the most common clinical symptoms in COVID-19 patients: a systematic review and meta‑analysis. J Prev Med Hyg. 2020; 61(3): E304–312.
8. Lin L, Jiang X, Zhang Z, et al. Gastrointestinal symptoms of 95 cases with SARS‑CoV-2 infection. Gut. 2020; 69: 997–1001.
9. Chen X, Laurent S, Oezguer AO, et al. A systematic review of neurological symptoms and complications of COVID-19. Journal of Neurology. 2021; 268: 392–402.
10. Odriozola‑Gonzalez P, Planchuelo‑Gómez Á, Jesús Irurtia M, de Luis‑García R. Psychological symptoms of the outbreak of the COVID-19 confinement in Spain. Journal of Health Psychology. 2022; 27(4): 825–835.
11. Team CDCC 19 R. SARS‑CoV-2 B.1. 1. 529 (Omicron) Variant - United States, December 1-8, 2021. MMWR Morb Mortal Wkly Rep. 2021; 70(50): 1731–1734.
12. Beyerstedt S, Casaro EB, Rangel ÉB. COVID-19: angiotensin‑converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS‑CoV-2 infection. European Journal of Clinical Microbiology & Infectious Diseases. 2021; 40(5): 905–919.
13. Seymen CM. The other side of COVID-19 pandemic: Effects on male fertility. 2020; 93(3): 1396–1402.
14. Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression pro¢ling of ACE 2, a novel homologue of angiotensin converting enzyme. 2002; 532(1-2): 107–110.
15. Li W, Moore MJ, Vasilieva N, et al. Angiotensin‑converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003; 426(6965): 450–454.
16. Sengupta P, Dutta S, Slama P, Roychoudhury S. COVID-19, oxidative stress, and male reproductive dysfunctions: is vitamin C a potential remedy? Physiol Res. 2022; 71(1): 47–54.
17. Jian S, Yushun W, Chuming L, et al. Cell entry mechanisms of SARS‑CoV-2. Proceedings of the National Academy of Sciences. 2020; 117(21): 11727–11734.
18. Younis JS, Abassi Z, Skorecki K. Is there an impact of the COVID-19 pandemic on male fertility? The ACE2 connection. American Journal of Physiology‑Endocrinology and Metabolism. 2020; 318(6): E878–880.
19. Douglas GC, O’Bryan MK, Hedger MP, et al. The novel Angiotensin‑Converting Enzyme (ACE) homolog, ACE2, is selectively expressed by adult leydig cells of the testis. Endocrinology. 2004; 145(10): 4703–4711.
20. Reis AB, Fabiano CA, Pereira VM, et al. Angiotensin (1–7) and its receptor Mas are expressed in the human testis: implications for male infertility. 2010; 41(1): 75–80
21. Liu X, Chen Y, Tang W, et al. Single‑cell transcriptome analysis of the novel coronavirus (SARS‑CoV-2) associated gene ACE2 expression in normal and non‑obstructive
azoospermia (NOA) human male testes. Science China Life Sciences. 2020; 63(7): 1006–1015.
22. Wang K, Chen W, Zhou YS, et al. SARS‑CoV-2 invades host cells via a novel route: CD147-spike protein.BioRxiv. 2020.
23. Cantuti‑Castelvetri L, Ojha R, Pedro LD, et al. Neuropilin-1 facilitates SARS‑CoV-2 cell entry and provides a possible pathway into the central nervous system. BioRxiv. 2020.
24. Yang M, Chen S, Huang B, et al. Pathological Findings in the Testes of COVID-19 Patients: Clinical Implications. Eur Urol Focus. 2020; 6(5): 1124–1129.
25. Flaifel A, Guzzetta M, Occidental M, et al. Testicular Changes Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‑CoV-2). Archives of Pathology & Laboratory Medicine. 2020; 145(1): 8–9.
26. Li H, Xiao X, Zhang J, et al. Impaired spermatogenesis in COVID-19 patients. EClinicalMedicine. 2020; 28: 100604.
27. Xu J, Qi L, Chi X, et al. Orchitis: A Complication of Severe Acute Respiratory Syndrome (SARS)1. Biology of Reproduction. 2006; 74(2): 410–416.
28. Pan F, Xiao X, Guo J, et al. No evidence of severe acute respiratory syndrome–coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertil Steril. 2020; 113(6): 1135–1139.
29. Moghimi N, Eslami Farsani B, Ghadipasha M, et al. COVID-19 disrupts spermatogenesis through the oxidative stress pathway following induction of apoptosis. Apoptosis. 2021; 26(7): 415–430.
30. Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nature Reviews Immunology. 2020; 20(6): 363–374.
31. Ediz C, Tavukcu HH, Akan S, et al. Is there any association of COVID-19 with testicular pain and epididymo‑orchitis? International Journal of Clinical Practice. 2021; 75(3): e13753.
32. Qingqing C, Wen QH, Ming Z, Huijun L, Zhen FF. Enhancement of Blood‑Brain Barrier Permeability and Reduction of Tight Junction Protein Expression Are Modulated by Chemokines/Cytokines Induced by Rabies Virus Infection. Journal of Virology. 2014; 88(9): 4698–4710.
33. Vishvkarma R, Rajender S. Could SARS‑CoV-2 affect male fertility? Andrologia. 2020; 52(9): e13712–e13712.
34. Ma L, Xie W, Li D, et al. Evaluation of sex‑related hormones and semen characteristics in reproductive‑aged male COVID-19 patients. Journal of Medical Virology. 2021; 93(1): 456–462.
35. Ma L, Xie W, Li D, et al. Effect of SARS‑CoV-2 infection upon male gonadal function: a single center‑based study. medRxiv. 2020.
36. Tian Y, Zhou L quan. Evaluating the impact of COVID-19 on male reproduction. Reproduction. 2021; 161(2): 37–44.
37. Pazir Y, Eroglu T, Kose A, et al. Impaired semen parameters in patients with confirmed SARS‑CoV-2 infection: A prospective cohort study. Andrologia. 2021; 53(9): e14157.
38. Collodel G, Capitani S, Pammolli A, et al. Semen Quality of Male Idiopathic Infertile Smokers and Nonsmokers: An Ultrastructural Study. Journal of Andrology. 2010; 31(2): 108–113.
39. World Health Organization, editor. WHO laboratory manual for the examination and processing of human semen. 6th ed. Geneva, Switzerland; 2021.
40. Guo L, Zhao S, Li W, et al. Absence of SARS‑CoV-2 in semen of a COVID-19 patient cohort. Andrology. 2021; 9(1): 42–47.
41. Song H, Seddighzadeh B, Cooperberg MR, Huang FW. Expression of ACE2, the SARS‑CoV-2 Receptor, and TMPRSS2 in Prostate Epithelial Cells. Eur Urol. 2020; 78(2): 296–298.
42. Massarotti C, Garolla A, Maccarini E, et al. SARS-CoV-2 in the semen: Where does it come from? Andrology. 2021; 9(1): 39–41.
43. Wang Z, Xu X. scRNA‑seq profiling of human testes reveals the presence of the ACE2 receptor, a target for SARS‑CoV-2 infection in spermatogonia, Leydig and Sertoli cells. Cells. 2020; 9(4): 920.
44. Aitken RJ. COVID-19 and male infertility: An update. Andrology. 2022.
Štítky
Paediatric urologist Nephrology UrologyČlánok vyšiel v časopise
Czech Urology
2022 Číslo 4
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