The Possible Role of SARS-CoV-2 in Male Fertility: A Narrative Review
Abstract
:1. Introduction
1.1. Angiotensin-Converting Enzyme Receptor 2 and Testis
1.2. Orchitis and Autoimmunity
1.3. SARS-CoV-2 in Semen and Sperm Parameters in COVID-19 Patients
1.4. Sex Hormone Levels
2. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
- Mongioì, L.M.; Barbagallo, F.; Condorelli, R.A.; Cannarella, R.; Aversa, A.; La Vignera, S.; Calogero, A.E. Possible long-term endocrine-metabolic complications in COVID-19: Lesson from the SARS model. Endocrine 2020, 68, 467–470. [Google Scholar] [CrossRef] [PubMed]
- Verrienti, P.; Cito, G.; Di Maida, F.; Tellini, R.; Cocci, A.; Minervini, A.; Natali, A. The impact of COVID-19 on the male genital tract: A qualitative literature review of sexual transmission and fertility implications. Clin. Exp. Reprod. Med. 2022, 49, 9–15. [Google Scholar] [CrossRef] [PubMed]
- Xu, X.; Chen, P.; Wang, J.; Feng, J.; Zhou, H.; Li, X.; Zhong, W.; Hao, P. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci. China Life Sci. 2020, 63, 457–460. [Google Scholar] [CrossRef]
- La Vignera, S.; Cannarella, R.; Condorelli, R.A.; Torre, F.; Aversa, A.; Calogero, A.E. Sex-Specific SARS-CoV-2 Mortality: Among Hormone-Modulated ACE2 Expression, Risk of Venous Thromboembolism and Hypovitaminosis D. Int. J. Mol. Sci. 2020, 21, 2948. [Google Scholar] [CrossRef]
- 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, 45. [Google Scholar] [CrossRef] [PubMed]
- Fu, J.; Zhou, B.; Zhang, L.; Balaji, K.S.; Wei, C.; Liu, X.; Chen, H.; Peng, J.; Fu, J. Expressions and significances of the angiotensin-converting enzyme 2 gene, the receptor of SARS-CoV-2 for COVID-19. Mol. Biol. Rep. 2020, 47, 4383–4392. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- Qio Shen, Q.; Xiao, X.; Aierken, A.; Yue, W.; Wu, X.; Liao, M.; Hua, J. The ACE2 expression in Sertoli cells and germ cells may cause male reproductive disorder after SARS-CoV-2 infection. J. Cell Mol. Med. 2020, 24, 9472–9477. [Google Scholar] [CrossRef]
- Seymen, C.M. The other side of COVID-19 pandemic: Effects on male fertility. J. Med. Virol. 2021, 93, 1396–1402. [Google Scholar] [CrossRef]
- Reis, A.B.; Araújo, F.C.; Pereira, V.M.; Dos Reis, A.M.; Santos, R.A.; Reis, F.M. Angiotensin (1-7) and its receptor Mas are expressed in the human testis: Implications for male infertility. J. Mol. Histol. 2010, 41, 75–80. [Google Scholar] [CrossRef]
- Gianzo, M.; Muñoa-Hoyos, I.; Urizar-Arenaza, I.; Larreategui, Z.; Quintana, F.; Garrido, N.; Subirán, N.; Irazusta, J. Angiotensin II type 2 receptor is expressed in human sperm cells and is involved in sperm motility. Fertil. Steril. 2016, 105, 608–616. [Google Scholar] [CrossRef]
- Harmer, D.; Gilbert, M.; Borman, R.; Clark, K.L. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett. 2002, 4, 532. [Google Scholar] [CrossRef]
- Fan, C.; Li, K.; Ding, Y.; Lu, W.L.; Wang, J. ACE2 expression in kidney and testis may cause kidney and testis damage after 2019-nCoV infection. MedRxiv 2020. [Google Scholar] [CrossRef]
- Xu, J.; Qi, L.; Chi, X.; Yang, J.; Wei, X.; Gong, E.; Peh, S.; Gu, J. Orchitis: A complication of severe acute respiratory syndrome (SARS). Biol. Reprod. 2006, 74, 410–416. [Google Scholar] [CrossRef]
- 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, 903–906. [Google Scholar] [CrossRef]
- Ediz, C.; Tavukcu, H.H.; Akan, S.; Kizilkan, Y.E.; Alcin, A.; Oz, K.; Yilmaz, O. Is there any association of COVID-19 with testicular pain and epididymo-orchitis? Int. J. Clin. Pract. 2021, 75, e13753. [Google Scholar] [CrossRef]
- Achua, J.K.; Chu, K.Y.; Ibrahim, E.; Khodamoradi, K.; Delma, K.S.; Iakymenko, O.A.; Kryvenko, O.N.; Arora, H.; Ramasamy, R. Histopathology and Ultrastructural Findings of Fatal COVID-19 Infections on Testis. World J. Mens Health 2021, 39, 65–74. [Google Scholar] [CrossRef]
- Ma, X.; Guan, C.; Chen, R.; Wang, Y.; Feng, S.; Wang, R.; Qu, G.; Zhao, S.; Wang, F.; Wang, X.; et al. Pathological and molecular examinations of postmortem testis biopsies reveal SARS-CoV-2 infection in the testis and spermatogenesis damage in COVID-19 patients. Cell Mol. Immunol. 2021, 18, 487–489. [Google Scholar] [CrossRef]
- Li, H.; Xiao, X.; Zhang, J.; Zafar, M.I.; Wu, C.; Long, Y.; Lu, W.; Pan, F.; Meng, T.; Zhao, K.; et al. Impaired spermatogenesis in COVID-19 patients. EClinicalMedicine 2020, 28, 100604. [Google Scholar] [CrossRef] [PubMed]
- Mital, P.; Hinton, B.T.; Dufour, J.M. The blood-testis and blood-epididymis barriers are more than just their tight junctions. Biol. Reprod. 2011, 84, 851–858. [Google Scholar] [CrossRef] [Green Version]
- Mruk, D.D.; Cheng, C.Y. The Mammalian Blood-Testis Barrier: Its Biology and Regulation. Endocr. Rev. 2015, 36, 564–591. [Google Scholar] [CrossRef] [PubMed]
- Cui, D.; Han, G.; Shang, Y.; Liu, C.; Xia, L.; Li, L.; Yi, S. Antisperm antibodies in infertile men and their effect on semen parameters: A systematic review and meta-analysis. Clin. Chim. Acta 2015, 444, 29–36. [Google Scholar] [CrossRef] [PubMed]
- Donders, G.G.G.; Bosmans, E.; Reumers, J.; Donders, F.; Jonckheere, J.; Salembier, G.; Stern, N.; Jacquemyn, Y.; Ombelet, W.; Depuydt, C.E. Sperm quality and absence of SARS-CoV-2 RNA in semen after COVID-19 infection: A prospective, observational study and validation of the Sperm COVID test. Fertil. Steril. 2022, 117, 287–296. [Google Scholar] [CrossRef] [PubMed]
- Corona, G.; Vena, W.; Pizzocaro, A.; Pallotti, F.; Paoli, D.; Rastrelli, G.; Baldi, E.; Cilloni, N.; Gacci, M.; Semeraro, F.; et al. Andrological effects of SARS-Cov-2 infection: A systematic review and meta-analysis. J. Endocrinol. Investig. 2022, 9, 1–13. [Google Scholar] [CrossRef] [PubMed]
- Salam, A.P.; Horby, P.W. The Breadth of Viruses in Human Semen. Emerg. Infect. Dis. 2017, 23, 1922–1924. [Google Scholar]
- Gupta, P.; Leroux, C.; Patterson, B.K.; Kingsley, L.; Rinaldo, C.; Ding, M.; Chen, Y.; Kulka, K.; Buchanan, W.; McKeon, B.; et al. Human immunodeficiency virus type 1 shedding pattern in semen correlates with the compartmentalization of viral Quasi species between blood and semen. J. Infect. Dis. 2000, 182, 79–87. [Google Scholar] [CrossRef]
- Rubin, S.; Eckhaus, M.; Rennick, L.J.; Bamford, C.G.; Duprex, W.P. Molecular biology, pathogenesis and pathology of mumps virus. J. Pathol. 2015, 235, 242–252. [Google Scholar] [CrossRef]
- Guo, L.; Zhao, S.; Li, W.; Wang, Y.; Li, L.; Jiang, S.; Ren, W.; Yuan, Q.; Zhang, F.; Kong, F.; et al. Absence of SARS-CoV-2 in semen of a COVID-19 patient cohort. Andrology 2021, 9, 42–47. [Google Scholar] [CrossRef]
- Ruan, Y.; Hu, B.; Liu, Z.; Liu, K.; Jiang, H.; Li, H.; Li, R.; Luan, Y.; Liu, X.; Yu, G.; et al. No detection of SARS-CoV-2 from urine, expressed prostatic secretions, and semen in 74 recovered COVID-19 male patients: A perspective and urogenital evaluation. Andrology 2021, 9, 99–106. [Google Scholar] [CrossRef]
- Pan, F.; Xiao, X.; Guo, J.; Song, Y.; Li, H.; Patel, D.P.; Spivak, A.M.; Alukal, J.P.; Zhang, X.; Xiong, C.; et al. No evidence of severe acute respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertil. Steril. 2020, 113, 1135–1139. [Google Scholar] [CrossRef]
- Machado, B.; Barcelos Barra, G.; Scherzer, N.; Massey, J.; Dos Santos Luz, H.; Henrique Jacomo, R.; Herinques Santa Rita, T.; Davis, R. Presence of SARS-CoV-2 RNA in Semen-Cohort Study in the United States COVID-19 Positive Patients. Infect. Dis. Rep. 2021, 13, 12. [Google Scholar] [CrossRef] [PubMed]
- 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, e208292. [Google Scholar] [CrossRef] [PubMed]
- Temiz, M.Z.; Dincer, M.M.; Hacibey, I.; Yazar, R.O.; Celik, C.; Kucuk, S.H.; Alkurt, G.; Doganay, L.; Yuruk, E.; Muslumanoglu, A.Y. Investigation of SARS-CoV-2 in semen samples and the effects of COVID-19 on male sexual health by using semen analysis and serum male hormone profile: A cross-sectional, pilot study. Andrologia 2021, 53, e13912. [Google Scholar] [CrossRef]
- Carlsen, E.; Andersson, A.M.; Petersen, J.H.; Skakkebaek, N.E. History of febrile illness and variation in semen quality. Hum. Reprod. 2003, 18, 2089–2092. [Google Scholar] [CrossRef]
- Pazir, Y.; Eroglu, T.; Kose, A.; Bulut, T.B.; Genc, C.; Kadihasanoglu, M. Impaired semen parameters in patients with confirmed SARS-CoV-2 infection: A prospective cohort study. Andrologia 2021, 53, e14157. [Google Scholar] [CrossRef]
- Gacci, M.; Coppi, M.; Baldi, E.; Sebastianelli, A.; Zaccaro, C.; Morselli, S.; Pecoraro, A.; Manera, A.; Nicoletti, R.; Liaci, A.; et al. Semen impairment and occurrence of SARS-CoV-2 virus in semen after recovery from COVID-19. Hum. Reprod. 2021, 36, 1520–1529. [Google Scholar] [CrossRef]
- Hajizadeh Maleki, B.; Tartibian, B. COVID-19 and male reproductive function: A prospective, longitudinal cohort study. Reproduction 2021, 161, 319–331. [Google Scholar] [CrossRef]
- Best, J.C.; Kuchakulla, M.; Khodamoradi, K.; Lima, T.F.N.; Frech, F.S.; Achua, J.; Rosete, O.; Mora, B.; Arora, H.; Ibrahim, E.; et al. Evaluation of SARS-CoV-2 in Human Semen and Effect on Total Sperm Number: A Prospective Observational Study. World J. Mens Health 2021, 39, 489–495. [Google Scholar] [CrossRef]
- Guo, T.H.; Sang, M.Y.; Bai, S.; Ma, H.; Wan, Y.Y.; Jiang, X.H.; Zhang, Y.W.; Xu, B.; Chen, H.; Zheng, X.Y.; et al. Semen parameters in men recovered from COVID-19. Asian J. Androl. 2021, 23, 479–483. [Google Scholar]
- Purpura, L.J.; Alukal, J.; Chong, A.M.; Liu, L.; Cantos, A.; Shah, J.; Medrano, N.; Chang, J.Y.; Tsuji, M.; Mohri, H.; et al. SARS-CoV-2 RNA Shedding in Semen and Oligozoospermia of Patient with Severe Coronavirus Disease 11 Weeks after Infection. Emerg. Infect. Dis. 2022, 28, 196–200. [Google Scholar] [CrossRef]
- Delgado-Roche, L.; Mesta, F. Oxidative Stress as Key Player in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection. Arch. Med. Res. 2020, 51, 384–387. [Google Scholar] [CrossRef]
- Sengupta, P.; Dutta, S. Does SARS-CoV-2 infection cause sperm DNA fragmentation? Possible link with oxidative stress. Eur. J. Contracept. Reprod. Health Care 2020, 25, 405–406. [Google Scholar] [CrossRef]
- Condorelli, R.A.; La Vignera, S.; Barbagallo, F.; Alamo, A.; Mongioì, L.M.; Cannarella, R.; Aversa, A.; Calogero, A.E. Bio-Functional Sperm Parameters: Does Age Matter? Front. Endocrinol. 2020, 11, 558374. [Google Scholar] [CrossRef]
- Banihani, S.A. Human semen quality as affected by SARS-CoV-2 infection: An up-to-date review. Andrologia 2022, 54, e14295. [Google Scholar] [CrossRef]
- Nguyen, T.T.; Hulme, J.; Tran, H.D.; Vo, T.K.; Vo, G.V. The potential impact of COVID-19 on male reproductive health. J. Endocrinol. Investig. 2022, 45, 1483–1495. [Google Scholar] [CrossRef]
- Haghpanah, A.; Masjedi, F.; Alborzi, S.; Hosseinpour, A.; Dehghani, A.; Malekmakan, L.; Roozbeh, J. Potential mechanisms of SARS-CoV-2 action on male gonadal function and fertility: Current status and future prospects. Andrologia 2021, 53, e13883. [Google Scholar] [CrossRef]
- Salonia, A.; Pontillo, M.; Capogrosso, P.; Gregori, S.; Tassara, M.; Boeri, L.; Carenzi, C.; Abbate, C.; Cignoli, D.; Ferrara, A.M.; et al. Severely low testosterone in males with COVID-19: A case-control study. Andrology 2021, 9, 1043–1052. [Google Scholar] [CrossRef]
- Kadihasanoglu, M.; Aktas, S.; Yardimci, E.; Aral, H.; Kadioglu, A. SARS-CoV-2 Pneumonia Affects Male Reproductive Hormone Levels: A Prospective, Cohort Study. J. Sex. Med. 2021, 18, 256–264. [Google Scholar] [CrossRef]
- Ma, L.; Xie, W.; Li, D.; Shi, L.; Ye, G.; Mao, Y.; Xiong, Y.; Sun, H.; Zheng, F.; Chen, Z.; et al. Evaluation of sex-related hormones and semen characteristics in reproductive-aged male COVID-19 patients. J. Med. Virol. 2021, 93, 456–462. [Google Scholar] [CrossRef]
- Tan, C.; Huang, Y.; Shi, F.; Tan, K.; Ma, Q.; Chen, Y.; Jiang, X.; Li, X. C-reactive protein correlates with computed tomographic findings and predicts severe COVID-19 early. J. Med. Virol. 2020, 92, 856–862. [Google Scholar] [CrossRef] [Green Version]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Leanza, C.; Mongioì, L.M.; Cannarella, R.; La Vignera, S.; Condorelli, R.A.; Calogero, A.E. The Possible Role of SARS-CoV-2 in Male Fertility: A Narrative Review. Endocrines 2022, 3, 552-559. https://doi.org/10.3390/endocrines3030046
Leanza C, Mongioì LM, Cannarella R, La Vignera S, Condorelli RA, Calogero AE. The Possible Role of SARS-CoV-2 in Male Fertility: A Narrative Review. Endocrines. 2022; 3(3):552-559. https://doi.org/10.3390/endocrines3030046
Chicago/Turabian StyleLeanza, Claudia, Laura M. Mongioì, Rossella Cannarella, Sandro La Vignera, Rosita A. Condorelli, and Aldo E. Calogero. 2022. "The Possible Role of SARS-CoV-2 in Male Fertility: A Narrative Review" Endocrines 3, no. 3: 552-559. https://doi.org/10.3390/endocrines3030046