The possible effects of COVID-19 on the human reproductive system

Spike surface glycoprotein and small envelope matrix-nucleocapsid proteins, is from the Coronaviridae family and binds to host receptors via spike surface proteins. Although it shows its symptoms especially on the respiratory tract, various studies have been carried out considering that it also affects other systems in the body. For the virus to enter the host cell, it must bind to ACE2 (angiotensin converting enzyme 2). ACE2 is a key protein involved in balancing Ang I and Ang II levels. With receptors such as TMPRSS2 (transmembrane serine protease 2), the effects of the virus on the human reproductive system are much better understood. Since human germ cells and early embryos express ACE2, there is a potential risk of the Coronavirus associated with germ cells. Studies show that the coronavirus changes the amount and density of hormones in the human reproductive system. The fact that most of the partners of 35 female patients who had SARS-CoV-2 in the studies were infected individuals suggests that sexual transmission may be possible. It was determined that TMPRSS4, Cathepsin B and L, FURIN, MX1 and BSG gene expressions were high in the menstrual cycle, while ACE 2 and TMPRSS2 were moderately expressed. It has been shown that the ACE2 enzyme is most intensely expressed is the testes. Studies have shown that sperm DNA (deoxyribonucleic acid) fragmentation, changes in hormone levels and the formation of anti-sperm antibodies are an important cause of male infertility. Infected men have been found to have an impaired spermatogenesis. This rewiew; it aims to draw attention to the possible effects of the corona virus on the human reproductive system and to reveal new mechanisms for new research to be done.

Keywords:

COVID-19, human reproductive system ACE2, TMPRSS2,

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1. Adiga SK, Tholeti P, Uppangala S, Kalthur G, Gualtieri R, Talevi R. Fertility preservation during the COVID-19 pandemic: mitigating the viral contamination risk to reproductive cells in cryostorage. Reprod Biomed Online 2020;41:991-97.
2. Ai T, Yang Z, Hou H, Zhan C, Chen C, Lv W, et al. Correlation of chest CT and RT-PCR testing in Coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases. Radiology 2020;296:E32-40.
3. Aitken RJ. COVID-19 and human spermatozoa-Potential risks for infertility and sexual transmission? Andrology 2021;9:48-52.
4. Al-Lami RA, Urban RJ, Volpi E, Algburi AMA, Baillargeon J. Sex hormones and novel corona virus infectious disease (COVID-19). Mayo Clin Proc 2020;95:1710-14.
5. Balaman F, Tiryaki Hanbay S. [The Opinions of teachers about compulsory distance education due to Corona Virus (Covid-19)]. J Human Soc Sci Res 2021;10:52-84. [Article in Turkish]
6. Baratchian M, McManus JM, Berk M, Nakamura F, Mukhopadhyay S, Xu W, et al. Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes. Sci Rep 2021;11;11130.
7. Brewster UC, Perazella MA. The renin-angiotensin aldosterone system and the kidney: effects on kidney disease. Am J Med 2004;116:263-72.
8. Carluccio M, Soccio M, De Caterina R. Aspects of gene polymorphisms in cardiovascular disease: the renin-angiotensin system. Eur J Clin Invest 2001;31:476-88.
9. Cetintepe SP, İlhan MN. [Risk reduction in healthcare workers in the COVID-19 outbreak]. J Biotechnol Strategic Health Res 2020;1:50-4. [Article in Turkish]
10. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507-13.
11. Dolanbay EG, Yıldız A, Aydemir H, Acar S, Ersan H, Akar Y, et al. [COVID-19 threat to human reproductive system]. Acta Medic Nicomed 2022; 5:36-42. [Article in Turkish]
12. Guan WJ, Ni ZY, Hu Y, Deng L, Zhao Q, Wang H, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.
13. Hagaman JR, Moyer JS, Bachman ES, Sibony M, Maggar PL, Welch JE, et al. Angiotensin-converting enzyme and male fertility. P Natl A Sci 1998;95:2552-57.
14. Haghpanah A, Masjedi F, Alborzi S, Hosseinpour A, Dehghani A, Malekmakan L, et al. Potential mechanisms of SARS-CoV-2 action on male gonadal function and fertility: Current status and future prospects. Andrologia 2021;53:e13883.
15. Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett 2002;532(1-2):107-10.
16. Henarejos-Castillo I, Sebastian-Leon P, Devesa-Peiro A, Pellicer A, Diaz-Gimeno P. SARS-CoV-2 infection risk assessment in the endometrium: viral infection-related gene expression across the menstrual cycle. Fertil Steril 2020; 114:223-32.
17. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and blocked by a clinically proven protease inhibitor. Cell 2020;181:271-80.e8.
18. Huang HH, Wang PH, Yang YP, Chou SJ, Chu PW, Wu GJ, et al. A review of severe acute respiratory syndrome coronavirus 2 infection in the reproductive system. J Chin Med Assoc 2020;83:895-97.
19. Hyashi K, Acosta T, Tetsuka M, berisha B, Matsui M, Schams D, et al. Involvement of angiopoietin-Tie system in bovine follicular development and atresia: messenger RNA expression in theca interna and effect on steroid secretion. Biol Reprod 2003;69:2078-84.
20. Jing Y, Run-Qian L, Hao-Ran W, Hao-Ran C, Ya-Bin L, Yang G, et al. Potential influence of COVID-19/ACE2 on the female reproductive system. Mol Hum Reprod 2020;26:367-73.
21. Kyrou I, Karteris E, Robbins T, Chatha K, Drenos F, Randeva HS. Polycystic ovary syndrome (PCOS) and COVID-19: an overlooked female patient population at potentially higher risk during the COVID-19 pandemic. BMC Med 2020; 18:220.
22. Li MY, Li L, Zhang Y, Wang XS. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty 2020;9:23-9.
23. Li N, Wang T, Han D. Structural, cellular and molecular aspects of immune privilege in the testis. Front Immunol 2012;3:152.
24. Liu Y, Gayle AA, Wilder-Smith A, Rocklov J. The reproductive number of COVID-19 is higher compared to SARS coronavirus. J Travel Med 2020;27:taaa021.
25. Lonsdale J, Thomas J, Salvatore M, Phillips R, Lo E, Shad S, et al. The genotype-tissue expression (GTEx) project. Nat Genet 2013;45:580-5.
26. Madjunkov M, Dviri M, Librach C. A comprehensive review of the impact of COVID-19 on human reproductive biology, assisted reproduction care and pregnancy: a Canadian perspective. J Ovarian Res 2020;13:140.
27. Roy S, Kusari J, Soffer R, Lai C, Sen G. Isolation of cDNA clones of rabbit angiotensin converting enzyme: identification of two distinct mRNAs for the pulmonary and the testicular isozymes. Biochem Bioph Res Commun 1988;155:678-84.
28. Singh B, Gornet M, Sims H, Kisanga E, Knight Z, Segars S. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its effect on gametogenesis and early pregnancy. Am J Reprod Immunol 2020;84:e13351.
29. Mohammadi S, Abouzaripour M, Shariati NS, Shariati MBH. Ovarian vein thrombosis after coronavirus disease (COVID-19) infection in a pregnant woman: case report. J Thromb Thrombolysis 2020;50:604-7.
30. Speth RC, Daubert DL, Grove KL. Angiotensin II: a reproductive hormone too? Regul peptides 1999;79:25-40.
31. Sun J. The hypothesis that SARS-CoV-2 affects male reproductive ability by regulating autophagy. Med Hypotheses 2020;143:110083.
32. Tyrrell DA, Bynoe ML. Cultivation of viruses from a high proportion of patients with colds. Lancet 1966;1:76-7.
33. Vaz-Silva J, Carneiro MM, Ferreira MC, Pinheiro SVB, Silva DA, Silva-Filho AL, et al. The vasoactive peptide angiotensin-(1-7), its receptor Mas and the angiotensin-converting enzyme type 2 are expressed in the human endometrium. Reprod Sci 2009; 6:247-56.
34. Velavan TP, Meyer CG. The COVID-19 epidemic. Trop Med Int Health 2020;25:278-80.
35. Wang L, Wang Y, Ye D, Liu Q. A review of the 2019 Novel Coronavirus (COVID-19) based on current evidence. Int J Antimicrob Agents 2020;55:105948.
36. Wang Z, Xu X. scRNA-seq profiling of human testes reveals the presence of the ACE2 receptor, a target for SARSCoV-2 infection in spermatogonia, Leydig and Sertoli cells. Cells 2020;9:920.
37. Gagliardi L, Bertacca C, Centenari C, Merusi I, Parolo E, Ragazzo V, et al. Orchiepididymitis in a boy with COVID-19. Pediatr Infect Dis J 2020;39:e200-2
38. Zhang Y, Geng X, Tan Y, Li Q, Xu C, Xu J, et al. New understanding of the damage of SARS-CoV-2 infection outside the respiratory system. Biomed Pharmacother 2020;127:110195.
39. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579:270-3.