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The Journal "Obstetrics and Gynecology"Journal HistoryAims and ScopePolicies on Conflict of Interest, Human and Animal Rights, and Informed ConsentEditorial ProcessData sharing statementAdvertising PolicyThe Process for Handling Cases Requiring Corrections, Retractions, and Editorial Expressions of ConcernEditorial BoardEditorial CounsilInformation for ProfessionalsNewsContacts
ArchiveEthical StandardsSubscription
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Obstetrics and Gynegology2020№11
Effects of SARS-CoV-­2 on human...

Effects of SARS-CoV-­2 on human reproduction

DOI
https://dx.doi.org/10.18565/aig.2020.11.6-12

Dolgushin G.O., Romanov A.Yu.

1) M.V. Lomonosov Moscow State University, Moscow, Russia 2) Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow, Russia
The available information on the clinical features of COVID-19, the effects of the infection on various organs and systems, and the prevention and treatment is very limited and contradictory. There is especially little evidence for the effects of SARS-CoV-2 on the human reproductive system.
The authors carried out a systematic analysis of the data available in modern literature about the effects of the SARS-CoV-2 and COVID-19 on the female and male reproductive system and fertility. The literature review includes data from the publications available at https://pubmed.ncbi.nlm.nih.gov/ on this topic. The paper provides data on the etiology and pathogenesis of COVID-19, the ways of penetration into the human body, the possible mechanisms of damage to the gonads in males and females, and the available evidence of the effect of SARS-CoV-2 on human reproduction. Currently, there are no data proving the presence of infection of ovarian or endometrial tissues in women, which would affect oogenesis, embryo implantation, early embryogenesis, and the occurrence of pregnancy in natural cycles or in ART programs. It can be assumed that there may be the following disorders of the female reproductive system: ovarian tissue damage caused by SARS-CoV-2, which may contribute to ovulatory dysfunction; oocyte damage, which can facilitate the production of aneuploid oocytes; and endometrial cell damages, which can lead to impaired embryo implantation. The data on the effect of SARS-CoV-2 on spermatogenesis and testicular tissue damage are scanty and contradictory.
Conclusion. Further investigations are needed to study the effects of SARS-CoV-2 on human reproductive function.

Keywords

COVID-19
SARS-CoV-2
coronavirus
novel coronavirus infection
autoimmunity
reproductive system
ovaries
testes
gonadotoxicity
intrauterine infection
Full text (in Russian)

References

  1. Chan J.F.W., Kok K.H., Zhu Z., Chu H., To K.K.W., Yuan S., Yuen K.Y. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg. Microbes Infect. 2020; 9(1): 221-36. https://dx.doi.org/10.1080/22221751.2020.1719902.
  2. Paraskevis D., Kostaki E.G., Magiorkinis G., Panayiotakopoulos G., Sourvinos G., Tsiodras S. Full-genome evolutionary analysis of the novel corona virus(2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infect. Genet. Evol. 2020; 79: 104212. https://dx.doi.org/10.1016/j.meegid.2020.104212.
  3. Lu R., Zhao X., Li J., Niu P., Yang B., Wu H. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395(10224): 565-74. https://dx.doi.org/10.1016/S0140-6736(20)30251-8.
  4. Infantino M., Damiani A., Gobbi F.L., Grossi V., Lari B., Macchia D. et al. Serological assays for SARS-CoV-2 infectious disease: benefits, limitations and perspectives. Isr. Med. Assoc. J. 2020; 22(4): 203-10.
  5. Kirchdoerfer R.N., Cottrell C.A., Wang N., Pallesen J., Yassine H.M., Turner H.L. et al. Pre-fusion structure of a human coronavirus spike protein. Nature. 2016; 531(7592): 118-21. https://dx.doi.org/10.1038/nature17200.
  6. Ashour H.M., Elkhatib W.F., Rahman M.M., Elshabrawy H.A. Insights into the recent 2019 novel coronavirus (SARS-CoV-2) in light of past human coronavirus outbreaks. Pathogens. 2020; 9(3): 186. https://dx.doi.org/10.3390/pathogens9030186.
  7. Zhang H., Penninger J.M., Li Y., Zhong N., Slutsky A.S. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020; 46(4): 586-90. https://dx.doi.org/10.1007/s00134-020-05985-9.
  8. Li M.Y., Li L., Zhang Y., Wang X.S. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect. Dis. Poverty. 2020; 9(1): 45. https://dx.doi.org/10.1186/s40249-020-00662-x.
  9. 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. https://dx.doi.org/10.3390/cells9040920.
  10. Liu X., Chen Y., Tang W., Zhang L., Chen W., Yan Z. 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. Sci. China Life Sci. 2020; 63(7): 1006-15. https://dx.doi.org/10.1007/s11427-020-1705-0.
  11. Jing Y., Run-Qian L., Hao-Ran W., Hao-Ran C., Ya-Bin L., Yang G., Fei C. Potential influence of COVID-19/ACE2 on the female reproductive system. Mol. Hum. Reprod. 2020; 26(6): 367-73. https://dx.doi.org/10.1093/molehr/gaaa030.
  12. Stanley K.E., Thomas E., Leaver M., Wells D. Coronavirus disease-19 and fertility: viral host entry protein expression in male and female reproductive tissues. Fertil. Steril. 2020; 114(1): 33-43. https://dx.doi.org/10.1016/j.fertnstert.2020.05.001.
  13. Segars J., Katler Q., McQueen D.B., Kotlyar A., Glenn T., Knight Z. et al.; American Society for Reproductive Medicine Coronavirus/COVID-19 Task Force. Prior and novel coronaviruses, coronavirus disease 2019 (COVID-19), and human reproduction: what is known? Fertil. Steril. 2020; 113(6): 1140-9. https://dx.doi.org/10.1016/j.fertnstert.2020.04.025.
  14. Wang K., Chen W., Zhou Y.S., Lian J.Q., Zhang Z., Du P. et al. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein. BioRxiv. March 14 2020. https://dx.doi.org/10.1101/2020.03.14.988345.
  15. Guillot S., Delaval P., Brinchault G., Caulet-Maugendre S., Depince A., Lena H. et al. Increased extracellular matrix metalloproteinase inducer (EMMPRIN) expression in pulmonary fibrosis. Exp. Lung Res. 2006; 32(3-4): 81-97. https://dx.doi.org/10.1080/01902140600710512.
  16. Smedts A.M., Lele S.M., Modesitt S.C., Curry T.E. Expression of an extracellular matrix metalloproteinase inducer (basigin) in the human ovary and ovarian endometriosis. Fertil. Steril. 2006; 86(3): 535-42. https://dx.doi.org/10.1016/j.fertnstert.2006.01.042.
  17. Li K., Nowak R.A. The role of basigin in reproduction. Reproduction. 2019; Sep 1: REP-19-0268.R1. https://dx.doi.org/10.1530/REP-19-0268.
  18. Zupin L., Pascolo L., Zito G., Ricci G., Crovella S. SARS-CoV-2 and the next generations: which impact on reproductive tissues? J. Assist. Reprod. Genet. 2020; 37(10): 2399-403. https://dx.doi.org/10.1007/s10815-020-01917-0.
  19. Aassve A., Cavalli N., Mencarini L., Plach S., Livi Bacci M. The COVID-19 pandemic and human fertility. Science. 2020; 369(6502): 370-1. https://dx.doi.org/10.1126/science.abc9520.
  20. Blumenfeld Z. Possible impact of COVID-19 on fertility and assisted reproductive technologies. Fertil. Steril. 2020; 114(1): 56-7. https://dx.doi.org/10.1016/j.fertnstert.2020.05.023.
  21. Anifandis G., Messini C.I., Daponte A., Messinis I.E. COVID-19 and fertility: a virtual reality. Reprod. Biomed. Online. 2020; 41(2): 157-9. https://dx.doi.org/10.1016/j.rbmo.2020.05.001.
  22. Vaz-Silva J., Carneiro M.M., Ferreira M.C., Pinheiro S.V.B., Silva D.A., Silva A.L. 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; 16(3): 247-56. https://dx.doi.org/10.1177/1933719108327593.
  23. Cui P., Chen Z., Wang T., Dai J., Zhang J., Ding T. et al. Clinical features and sexual transmission potential of SARS-CoV-2 infected female patients: a descriptive study in Wuhan, China. medRxiv. February 26 2020. https://dx.doi.org/10.1101/2020.02.26.20028225.
  24. Valdés G., Neves L.A., Anton L., Corthorn J., Chacón C., Germain A.M. et al. Distribution of angiotensin-(1-7) and ACE2 in human placentas of normal and pathological pregnancies. Placenta. 2006; 27(2-3): 200-7. https://dx.doi.org/10.1016/j.placenta.2005.02.015.
  25. Zeng L., Xia S., Yuan W., Yan K., Xiao F., Shao J., Zhou W. Neonatal early-onset infection with SARS-CoV-2 in 33 neonates born to mothers with COVID-19 in Wuhan, China. JAMA Pediatr. 2020; 174(7): 722-5. https://dx.doi.org/10.1001/jamapediatrics.2020.0878.
  26. Dong L., Tian J., He S., Zhu C., Wang J., Liu C., Yang J. Possible vertical transmission of SARS-CoV-2 from an infected mother to her newborn. JAMA. 2020; 323(18): 1846-8. https://dx.doi.org/10.1001/jama.2020.4621.
  27. Wu Y.T., Liu C., Dong L., Zhang C.J., Chen Y., Liu J. et al. Viral shedding of COVID-19 in pregnant women. 27 March 2020. Available at: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3562059
  28. Yan R., Zhang Y., Li Y., Xia L., Guo Y., Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020; 367(6485): 1444-8. https://dx.doi.org/10.1126/science.abb2762.
  29. 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 is blocked by a clinically proven protease inhibitor. Cell. 2020; 181(2): 271-80. e8. https://dx.doi.org/10.1016/j.cell.2020.02.052.
  30. Wang X., Dhindsa R., Povysil G., Zoghbi A., Motelow J., Hostyk J. et al. Transcriptional inhibition of host viral entry proteins as a therapeutic strategy for SARSCoV-2. March 2020. https://dx.doi.org/10.20944/preprints202003.0360.v1. Available at: https://www.preprints.org/manuscript/202003.0360/v1
  31. Qi J., Zhou Y., Hua J., Zhang L., Bian J., Liu B. et al. The scRNA-seq expression profiling of the receptor ACE2 and the cellular protease TMPRSS2 reveals human organs susceptible to COVID-19 infection. BioRxiv. April 2020. https://dx.doi.org/10.1101/2020.04.16.045690. Available at: https:// www.biorxiv.org/content/10.1101/20
  32. Scorzolini L., Corpolongo A., Castilletti C., Lalle E., Mariano A., Nicastri E. Comment of the potential risks of sexual and vertical transmission of Covid-19 infection. Clin. Infect. Dis. 2020 April 16: ciaa445. https://dx.doi.org/10.1093/cid/ciaa445.
  33. Payne K., Kenny P., Scovell J.M., Khodamoradi K., Ramasamy R. Twenty-first century viral pandemics: a literature review of sexual transmission and fertility implications in men. Sex. Med. Rev. 2020; 8(4): 518-30. https://dx.doi.org/10.1016/j.sxmr.2020.06.003.
  34. Cardona Maya W.D., Du Plessis S.S., Velilla P.A. SARS-CoV-2 and the testis: similarity with other viruses and routes of infection. Reprod. Biomed. Online. 2020; 40(6): 763-4. https://dx.doi.org/10.1016/j.rbmo.2020.04.009.
  35. Chen Y., Guo Y., Pan Y., Zhao Z.J. Structure analysis of the receptor binding of 2019-nCoV. Biochem. Biophys. Res. Commun. 2020; 525(1): 135-40. https://dx.doi.org/10.1016/j.bbrc.2020.02.071.
  36. Dutta S., Sengupta P. SARS-CoV-2 and male infertility: possible multifaceted pathology. Reprod. Sci. 2020 July 10: 1-4. https://dx.doi.org/10.1007/s43032-020-00261-z.
  37. Sun J. The hypothesis that SARS-CoV-2 affects male reproductive ability by regulating autophagy. Med. Hypotheses. 2020 October; 143: 110083. https://dx.doi.org/10.1016/j.mehy.2020.110083.
  38. Dong D., Fan T., Ji Y., Yu J., Wu S., Zhang L. Spironolactone alleviates diabetic nephropathy through promoting autophagy in podocytes. Int. Urol. Nephrol. 2019; 51(4): 755-64. https://dx.doi.org/10.1007/s11255-019-02074-9.
  39. Lai L., Chen J., Wang N., Zhu G., Duan X., Ling F. MiRNA-30e mediated cardioprotection of ACE2 in rats with Doxorubicin-induced heart failure through inhibiting cardiomyocytes autophagy. Life Sci. 2017; 169: 69-75. https://dx.doi.org/10.1016/j.lfs.2016.09.006.
  40. Li D., Jin M., Bao P., Zhao W., Zhang S. Clinical characteristics and results of semen tests among men with coronavirus disease 2019. JAMA Netw. Open. 2020; 3(5): e208292. https://dx.doi.org/10.1001/jamanetworkopen.2020.8292.
  41. Pan F., Xiao X., Guo J., Song Y., Li H., Patel D.P. 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): 1135-9. 10.1016/j.fertnstert.2020.04.024.
  42. Pavone C., Giammanco G.M., Baiamonte D., Pinelli M., Bonura C., Montalbano M. et al. Italian males recovering from mild COVID-19 show no evidence of SARS-CoV-2 in semen despite prolonged nasopharyngeal swab positivity. Int. J. Impot. Res. 2020; 32(5): 560-2. https://dx.doi.org/10.1038/s41443-020-00344-0.
  43. Song C., Wang Y., Li W., Hu B., Chen G., Xia P. et al. Absence of 2019 novel coronavirus in semen and testes of COVID-19 patients†. Biol. Reprod. 2020; 103(1): 4-6. https://dx.doi.org/10.1093/biolre/ioaa050.
  44. Paoli D., Pallotti F., Colangelo S., Basilico F., Mazzuti L., Turriziani O. et al. Study of SARS-CoV-2 in semen and urine samples of a volunteer with positive naso-pharyngeal swab. J. Endocrinol. Invest. 2020; Apr 23: 1-4. https://dx.doi.org/10.1007/s40618-020-01261-1.
  45. Holtmann N., Edimiris P., Andree M., Doehmen C., Baston-Buest D., Adams O. et al. Assessment of SARS-CoV-2 in human semen—a cohort study. Fertil. Steril. 2020;1 14 (2): 233-8. https://dx.doi.org/10.1016/j.fertnstert.2020.05.028.
  46. Xu J., Qi L., Chi X., Yang J., Wei X., Gong E. et al. Orchitis: a complication of severe acute respiratory syndrome (SARS). Biol. Reprod. 2006; 74(2): 410-6. https://dx.doi.org/10.1095/biolreprod.105.044776.
  47. Sigurdardóttir O.G., Kolbjørnsen O., Lutz H. Orchitis in a cat associated with coronavirus infection. J. Comp. Pathol. 2001; 124(2-3): 219-22. https://dx.doi.org/10.1053/jcpa.2000.0443.
  48. La Marca A., Busani S., Donno V., Guaraldi G., Ligabue G., Girardis M. Testicular pain as an unusual presentation of COVID-19: a brief review of SARS-CoV-2 and the testis. Reprod. Biomed. Online. 2020; 41(5): 903-6. https://dx.doi.org/10.1016/j.rbmo.2020.07.017.
  49. Ma L., Xie W., Li D., Shi L., Ye G., Mao Y. et al. Evaluation of sex-related hormones and semen characteristics in reproductive-aged male COVID-19 patients. J. Med. Virol. July 4 2020. https://dx.doi.org/10.1002/jmv.26259.

Received 31.08.2020

Accepted 03.09.2020

About the Authors

Grigory O. Dolgushin, student of Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University. Tel.: +7(916)215-97-13. E-mail: grdolgushin@yandex.ru.
31-5 Lomonosovsky Prospekt, 117192, Moscow, Russia.
Andrey Yu. Romanov, MD, Researcher of R&D Department, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology,
Ministry of Healthcare of the Russian Federation. Tel.:+7(903)158-94-00. E-mail: romanov1553@yandex.ru. 4 Academica Oparina str., 117997, Moscow, Russia.

For citation: Dolgushin G.O., Romanov A.Yu. Effects of SARS-COV-2 on human reproduction.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2020; 11: 6-12 (in Russian).
https://dx.doi.org/10.18565/aig.2020.11.6-12

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