Article Data

  • Views 483
  • Dowloads 144

Mini-Review

Open Access

Exploring spermatogenesis post-SARS-CoV-2: a comprehensive review of male reproductive health

  • Aamir Javed1
  • Manjula Kannasandra Ramaiah1,*,
  • Kamal Saba2

1Department of Biotechnology, REVA University, 560064 Bangalore, India

2Academy of Scientific and Innovative Research (AcSIR), 201002 Ghaziabad, India

DOI: 10.22514/jomh.2024.034 Vol.20,Issue 3,March 2024 pp.14-24

Submitted: 04 November 2023 Accepted: 06 December 2023

Published: 30 March 2024

*Corresponding Author(s): Manjula Kannasandra Ramaiah E-mail: drkrmanjula@gmail.com

Abstract

The global health crisis induced by the COVID-19 pandemic, due to the novel SARS-CoV-2 pathogen, has cast widespread implications on public health, notably impacting the male fertility. This review intends to consolidate and analyze academic research up to the conclusion of 2021, highlighting the potential consequences of SARS-CoV-2 within the scope of reproductive health of male. This review scrutinizes potential underlying mechanisms, with a thorough look at the pertinent biochemical and physiological pathways that could be implicated, drawing upon evidence from both clinical and pre-clinical investigations. Furthermore, it considers the potential long-term consequences of these alterations in relation to assisted reproductive technologies. The precise effects of the severe respiratory condition, COVID-19, triggered by SARS-CoV-2, on fertility are still under investigation. Various potential risk factors have been identified that may link SARS-CoV-2 infection to complications in fertility. One such element is the presence of angiotensin-converting enzyme-2, the key receptor for viral entry, in the cells of the testes. This could potentially facilitate direct viral invasion, leading to subsequent damage. The evaluation of existing data is crucial in understanding the extensive effects of COVID-19, particularly in the sphere of family planning and management of reproductive health in the context of worldwide health crises. This review also intensifies gaps in our present understanding, suggesting areas for future exploration to more thoroughly understand the complex relationship between male reproductive health and SARS-CoV-2.


Keywords

ACE2 inhibitor; Fertility; Male; Semen; SARS-CoV-2


Cite and Share

Aamir Javed,Manjula Kannasandra Ramaiah,Kamal Saba. Exploring spermatogenesis post-SARS-CoV-2: a comprehensive review of male reproductive health. Journal of Men's Health. 2024. 20(3);14-24.

References

[1] Di Gennaro F, Pizzol D, Marotta C, Antunes M, Racalbuto V, Veronese N, et al. Coronavirus diseases (COVID-19) current status and future perspectives: a narrative review. International Journal of Environmental Research and Public Health. 2020; 17: 2690.

[2] Baloch S, Baloch MA, Zheng T, Pei X. The coronavirus disease 2019 (COVID-19) pandemic. The Tohoku Journal of Experimental Medicine. 2020; 250: 271–278.

[3] Mungroo MR, Khan NA, Siddiqui R. Novel coronavirus: current understanding of clinical features, diagnosis, pathogenesis, and treatment options. Pathogens. 2020; 9: 297.

[4] Eisenberg ML. Coronavirus disease 2019 and men’s reproductive health. Fertility and Sterility. 2020; 113: 1154.

[5] Carlsen E, Andersson AM, Petersen JH, Skakkebaek NE. History of febrile illness and variation in semen quality. Human Reproduction. 2003; 18: 2089–2092.

[6] Batiha O, Al-Deeb T, Al-Zoubi E, Alsharu E. Impact of COVID-19 and other viruses on reproductive health. Andrologia. 2020; 52: e13791.

[7] Adhikari SP, Meng S, Wu Y, Mao Y, Ye R, Wang Q, et al. Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review. Infectious Diseases of Poverty. 2020; 9: 29.

[8] 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: 271–280.e8.

[9] Dutta S, Sengupta P. SARS-CoV-2 and male infertility: possible multifaceted pathology. Reproductive Sciences. 2021; 28: 23–26.

[10] Zhao S, Zhu W, Xue S, Han D. Testicular defense systems: immune privilege and innate immunity. Cellular & Molecular Immunology. 2014; 11: 428–437.

[11] Pan F, Xiao X, Guo J, Song Y, Li H, Patel DP, et al. No evidence of severe acute respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertility and Sterility. 2020; 113: 1135–1139.

[12] Pallotti F, Esteves SC, Faja F, Buonacquisto A, Conflitti AC, Hirsch MN, et al. COVID-19 and its treatments: lights and shadows on testicular function. Endocrine. 2023; 79: 243–251.

[13] Javed A, Talkad MS, Ramaiah MK. Evaluation of sperm DNA fragmentation using multiple methods: a comparison of their predictive power for male infertility. Clinical and Experimental Reproductive Medicine. 2019; 46: 14–21.

[14] Xu J, Qi L, Chi X, Yang J, Wei X, Gong E, et al. Orchitis: a complication of severe acute respiratory syndrome (SARS). Biology of Reproduction. 2006; 74: 410–416.

[15] Shi S, Hu H, Wang J, Huang X, Li J, Li D. Evaluation of semen DNA integrity and related parameters with COVID-19 infection: a prospective cohort study. Virology journal. 2023; 20: 218.

[16] Khalili MA, Leisegang K, Majzoub A, Finelli R, Panner Selvam MK, Henkel R, et al. Male fertility and the COVID-19 pandemic: systematic review of the literature. The World Journal of Men’s Health. 2020; 38: 506–520.

[17] 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.

[18] Caliskan Z, Kucukgergin C, Aktan G, Kadioglu A, Ozdemirler G. Evaluation of sperm DNA fragmentation in male infertility. Andrologia. 2022; 54: e14587.

[19] Dipankar SP, Kumar T, Itagi ABH, Naik BN, Kumar Y, Sharma M, et al. Semen quality in males suffering from COVID-19: a pilot study. Cureus. 2022; 14: e31776.

[20] 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: 920.

[21] Shen Q, Xiao X, Aierken A, Yue W, Wu X, Liao M, et al. The ACE2 expression in Sertoli cells and germ cells may cause male reproductive disorder after SARS-CoV-2 infection. Journal of Cellular and Molecular Medicine. 2020; 24: 9472–9477.

[22] Glowacka I, Bertram S, Müller MA, Allen P, Soilleux E, Pfefferle S, et al. Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. Journal of Virology. 2011; 85: 4122–4134.

[23] Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. Addendum: a pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 588: E6.

[24] Boopathi S, Poma AB, Kolandaivel P. Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment. Journal of Biomolecular Structure and Dynamics. 2021; 39: 3409–3418.

[25] Jiang S, Hillyer C, Du L. Neutralizing antibodies against SARS-CoV-2 and other human coronaviruses. Trends in Immunology. 2020; 41: 355–359.

[26] Wiener RS, Cao YX, Hinds A, Ramirez MI, Williams MC. Angiotensin converting enzyme 2 is primarily epithelial and is developmentally regulated in the mouse lung. Journal of Cellular Biochemistry. 2007; 101: 1278–1291.

[27] Pinto BGG, Oliveira AER, Singh Y, Jimenez L, Gonçalves ANA, Ogava RLT, et al. ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19. The Journal of Infectious Diseases. 2020; 222: 556–563.

[28] Li L, Sottas CM, Chen HY, Li Y, Cui H, Villano JS, et al. SARS-CoV-2 enters human leydig cells and affects testosterone production in vitro. Cells. 2023; 12: 1198.

[29] Segars J, Katler Q, McQueen DB, Kotlyar A, Glenn T, Knight Z, et al. Prior and novel coronaviruses, coronavirus disease 2019 (COVID-19), and human reproduction: what is known? Fertility and Sterility. 2020; 113: 1140–1149.

[30] Dinnes J, Sharma P, Berhane S, van Wyk SS, Nyaaba N, Domen J, et al. Rapid, point-of-care antigen tests for diagnosis of SARS-CoV-2 infection. Cochrane Database of Systematic Reviews. 2022; 7: CD013705.

[31] Zhou G, Chen S, Chen Z. Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies. Frontiers of Medicine. 2020; 14: 117–125.

[32] Richardson ET, Malik MM, Darity WA, Mullen AK, Morse ME, Malik M, et al. Reparations for Black American descendants of persons enslaved in the U.S. and their potential impact on SARS-CoV-2 transmission. Social Science & Medicine. 2021; 276: 113741.

[33] Stanley KE, Thomas E, Leaver M, Wells D. Coronavirus disease-19 and fertility: viral host entry protein expression in male and female reproductive tissues. Fertility and Sterility. 2020; 114: 33–43.

[34] Esteves SC, Lombardo F, Garrido N, Alvarez J, Zini A, Colpi GM, et al. SARS-CoV-2 pandemic and repercussions for male infertility patients: a proposal for the individualized provision of andrological services. Andrology. 2021; 9: 10–18.

[35] Paoli D, Pallotti F, Nigro G, Mazzuti L, Hirsch MN, Valli MB, et al. Molecular diagnosis of SARS-CoV-2 in seminal fluid. Journal of Endocrinological Investigation. 2021; 44: 2675–2684.

[36] Corona G, Vena W, Pizzocaro A, Pallotti F, Paoli D, Rastrelli G, et al. Andrological effects of SARS-CoV-2 infection: a systematic review and meta-analysis. Journal of Endocrinological Investigation. 2022; 45: 2207–2219.

[37] Xia J, Tong J, Liu M, Shen Y, Guo D. Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection. Journal of Medical Virology. 2020; 92: 589–594.

[38] 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 SARS-CoV-2 infection. International Journal of Environmental Research and Public Health. 2021; 18: 284.

[39] Pike JFW, Polley EL, Pritchett DY, Lal A, Wynia BA, Roudebush WE, et al. Comparative analysis of viral infection outcomes in human seminal fluid from prior viral epidemics and Sars-CoV-2 may offer trends for viral sexual transmissibility and long-term reproductive health implications. Reproductive Health. 2021; 18: 123.

[40] Devaux CA, Rolain J, Raoult D. ACE2 receptor polymorphism: susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome. Journal of Microbiology, Immunology and Infection. 2020; 53: 425–435.

[41] Abobaker A, Raba AA. Does COVID-19 affect male fertility? World Journal of Urology. 2021; 39: 975–976.

[42] Bridwell RE, Merrill DR, Griffith SA, Wray J, Oliver JJ. A coronavirus disease 2019 (COVID-19) patient with bilateral orchitis. The American Journal of Emergency Medicine. 2021; 42: 260.e3–260.e5.

[43] Kharbach Y, Khallouk A. Male genital damage in COVID-19 patients: are available data relevant? Asian Journal of Urology. 2021; 8: 324–326.

[44] Amparore D, Campi R, Checcucci E, Sessa F, Pecoraro A, Minervini A, et al. Forecasting the future of urology practice: a comprehensive review of the recommendations by international and European associations on priority procedures during the COVID-19 pandemic. European Urology Focus. 2020; 6: 1032–1048.

[45] Salamanna F, Maglio M, Landini MP, Fini M. Body localization of ACE-2: on the trail of the keyhole of SARS-CoV-2. Frontiers in Medicine. 2020; 7: 594495.

[46] Edenfield RC, Easley CA. Implications of testicular ACE2 and the renin–angiotensin system for SARS-CoV-2 on testis function. Nature Reviews Urology. 2022; 19: 116–127.

[47] Sharma A, Tiwari S, Deb MK, Marty JL. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): a global pandemic and treatment strategies. International Journal of Antimicrobial Agents. 2020; 56: 106054.

[48] Ly J, Campos RK, Hager-Soto EE, Camargos VN, Rossi SL. Testicular pathological alterations associated with SARS-CoV-2 infection. Frontiers in Reproductive Health. 2023; 5: 1229622.

[49] Rastrelli G, Di Stasi V, Inglese F, Beccaria M, Garuti M, Di Costanzo D, et al. Low testosterone levels predict clinical adverse outcomes in SARS-CoV-2 pneumonia patients. Andrology. 2021; 9: 88–98.

[50] 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. Journal of Endocrinological Investigation. 2020; 43: 1819–1822.

[51] Li D, Jin M, Bao P, Zhao W, Zhang S. Clinical characteristics and results of semen tests among men with coronavirus disease 2019. JAMA Network Open. 2020; 3: e208292.

[52] Ling M, Wen X, Danyang L, Lei S, Yanhong M, Yao X, et al. Effect of SARS-CoV-2 infection upon male gonadal function: a single center-based study. To be published in medRχiv. 2020. [Preprint]

[53] Ning JL, Li W, Ruan Y, Xia YQ, Wu XF, Hu K, et al. Effects of 2019 novel coronavirus on male reproductive system: a retrospective study. To be published in Priprintsorg. 2020. [Preprint]

[54] 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. Biology of Reproduction. 2020; 103: 4–6.

[55] Maria Schroeder BT, Dominik J, Axel N, Tian B, Henning J, Martin Z, et al. The majority of male patients with COVID-19 present low testosterone levels on admission to intensive care in Hamburg, Germany: a retrospective cohort study. To be published in medRχiv. 2020. [Preprint]

[56] 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. Fertility and Sterility. 2020; 114: 233–238.

[57] Li H, Xiao X, Zhang J, Zafar MI, Wu C, Long Y, et al. Impaired spermatogenesis in COVID-19 patients. EClinicalMedicine. 2020; 28: 100604.

[58] Kadihasanoglu M, Aktas S, Yardimci E, Aral H, Kadioglu A. SARS-CoV-2 pneumonia affects male reproductive hormone levels: a prospective, cohort study. The Journal of Sexual Medicine. 2021; 18: 256–264.

[59] Okçelik S. COVID‐19 pneumonia causes lower testosterone levels. Andrologia. 2021; 53: e13909.

[60] Ediz C, Tavukcu HH, Akan S, Kizilkan YE, Alcin A, Oz K, et al. Is there any association of COVID-19 with testicular pain and epididymo-orchitis? International Journal of Clinical Practice. 2021; 75: e13753.

[61] Flaifel A, Guzzetta M, Occidental M, Najari BB, Melamed J, Thomas KM, et al. Testicular changes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Archives of Pathology & Laboratory Medicine. 2021; 145: 8–9.

[62] Hajizadeh Maleki B, Tartibian B. COVID-19 and male reproductive function: a prospective, longitudinal cohort study. Reproduction. 2021; 161: 319–331.

[63] Gacci M, Coppi M, Baldi E, Sebastianelli A, Zaccaro C, Morselli S, et al. Semen impairment and occurrence of SARS-CoV-2 virus in semen after recovery from COVID-19. Human Reproduction. 2021; 36: 1520–1529.

[64] Chen L, Huang X, Yi Z, Deng Q, Jiang N, Feng C, et al. Ultrasound imaging findings of acute testicular infection in patients with coronavirus disease 2019: a single-center-based study in Wuhan, China. Journal of Ultrasound in Medicine. 2021; 40: 1787–1794.

[65] He W, Liu X, Feng L, Xiong S, Li Y, Chen L, et al. Impact of SARS-CoV-2 on male reproductive health: a review of the literature on male reproductive involvement in COVID-19. Frontiers in Medicine. 2020; 7: 594364.

[66] Sengupta P, Leisegang K, Agarwal A. The impact of COVID-19 on the male reproductive tract and fertility: a systematic review. Arab Journal of Urology. 2021; 19: 423–436.


Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Directory of Open Access Journals (DOAJ) DOAJ is a unique and extensive index of diverse open access journals from around the world, driven by a growing community, committed to ensuring quality content is freely available online for everyone.

SCImago The SCImago Journal & Country Rank is a publicly available portal that includes the journals and country scientific indicators developed from the information contained in the Scopus® database (Elsevier B.V.)

Publication Forum - JUFO (Federation of Finnish Learned Societies) Publication Forum is a classification of publication channels created by the Finnish scientific community to support the quality assessment of academic research.

Scopus: CiteScore 0.7 (2022) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

Norwegian Register for Scientific Journals, Series and Publishers Search for publication channels (journals, series and publishers) in the Norwegian Register for Scientific Journals, Series and Publishers to see if they are considered as scientific. (https://kanalregister.hkdir.no/publiseringskanaler/Forside).

Submission Turnaround Time

Conferences

Top