Male reproductive system alterations by SARS-CoV-2 and its pathophysiology: A review

Authors

DOI:

https://doi.org/10.33448/rsd-v11i9.31727

Keywords:

Male fertility; Pandemics; Coronavirus; Angiotensin-converting enzyme 2.

Abstract

This integrative literature review aimed to analyze the findings about the SARS-CoV-2 action on the male genital tract. The database used in the search was PubMed, Scielo and Google Scholar with the following descriptors: “Male fertility”, “COVID-19”, “Infertility”, in addition to the use of the Boolean operator (AND). The final sample was 25 baseline studies. The entry of the coronavirus takes place through the interaction of its proteins with ACE-2 and TMPRSS2. Such proteins were identified in the male reproductive system, which explains several clinical findings in patients who were infected. This interaction of the virus with cells prevents the formation of Ang 1-7, which has anti-inflammatory properties, so its reduction would cause local tissue damage in the testicular tissue. Such findings ranged from histological changes with the formation of an inflammatory infiltrate to possible autoimmune orchitis. In addition, there are controversies on certain topics, such as the carriage of the virus in semen and its potential to cause embryological damage. The study showed the different pathophysiological possibilities of the virus in causing changes in male fertility, through the inflammatory effect, direct cytopathological action of the virus, fever, infections of other structures of the reproductive system, direct alterations in the hypothalamic pituitary axis and use of drugs as a treatment. All these results show the complexity of this virus in other systems and its mechanisms, which requires further studies for its full understanding.

References

Abdel-Moneim A (2021). COVID19 Pandemic and Male Fertility: Clinical Manifestations and Pathogenic Mechanisms. Biokhimiya, 86 (4), 459 - 468.

Abobaker, A., & Raba, A. A. (2021). Does COVID‑19 afect male fertility? World Journal of Urology., 39, 975-976.

Aitken, R. J. (2021). COVID-19 and male infertility: An update. Andrology., 10 (1), 8-10.

Batiha, O., Al-Deeb, T., Al-zoubi, E., & Alsharu, E. (2020). Impact of COVID-19 and other viruses on reproductive health. J. Andrology., 52 (9), 13791.

Corona, G., Baldi, E., Isidori, A. M., Paoli, D., Pallotti, F., Santis, L. D., Francavilla, F., Vignera, S. L., Selice, R., Caponecchia, L., Pivonello, R., Ferlin, A., Foresta, C., Jannini, E. A., Lenzi, A., Maggi, M., & Lombardo, F. (2020). SARS‑CoV‑2 infection, male fertility and sperm cryopreservation: a position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) (Società Italiana di Andrologia e Medicina della Sessualità). Journal of Endocrinological Investigation., 43, 1153-1157.

Delamuta, L. C., Monteleone, P. A., Ferreira-Filho, S. S., Heinrich-Oliveira, V., Soares-Júnior, J. M., Baracat, E. C., & Maciel, G. A. (2021). Coronavirus Disease 2019 and Human Reproduction: A Changing Perspective. Clinics., 76, e3032.

Duarte-Neto, A. N., Monteiro, R. A., Silva, L. F., Malheiros, D. M., Oliveira, E. P., Filho, J. T. , Pinho, J. R., Gomes-Gouvêa, M. S., Salles, A. P., Oliveira, I. R., Mauad, T., Saldiva, P. H., & Dolhnikoff, M. (2020). Pulmonary and systemic involvement of COVID‐19 assessed by ultrasound‐guided minimally invasive autopsy. Histopathology., 77 (2), 186-197.

Dutta, S., & Sengupta, P. (2021). SARS-CoV-2 and Male Infertility: Possible Multifaceted Pathology. Reproductive Sciences., 28, 23-26.

Entezami, F., Samama, M., Dejucq-Rainsford, N., & Bujan, L. (2020). SARS-CoV-2 and human reproduction: An open question. E Clin. Med., 25.

Fathi, M., Vakili, K., Aliaghaei, A., Nematollahi, S., Peirouvi, T., & Shalizar-Jalali, A. (2021) Coronavirus disease and male fertility: a systematic review. Middle East Fertility Society Journal., 26 (1), 26.

Figueredo, I. C. (2021). COVID-19 y fertilidad masculina. Rev Cubana Invest Bioméd., 40 (1).

Gacci, M., Coppi, M., Baldi, E., Sebastianelli, A., Zaccaro, C., Morselli, S.,Pecoraro, A., Manera, A., Nicoletti, R., Liaci, A., Bisegna, C., Gemma, L., Giancane, S., Pollini, S., Antonelli, A., Lagi, F., Marchiani, S., Dabizzi, S., Degl’Innocenti, S., Annunziato, F., Maggi, M., Vignozzi, L., Bartoloni, A., Rossolini, G. M., & Serni, S. (2021). Semen impairment and occurrence of SARS-CoV-2 virus in semen after recovery from COVID-19. Hum Reprod., 36 (6), 1520-1529.

Gagliardi, L., Bertacca, C., Centenari, C., Merusi, I., Parolo, E., Ragazzo, V., & Tarabella, V. (2020). Orchiepididymitis in a Boy With COVID-19. The Pediatric Infectious Disease Journal., 39 (8), 200-202.

Groner MF, Carvalho RC, Camillo J, Ferreira PR, Fraietta R (2021). Effects of Covid-19 on male reproductive system. Braz j urol., 47.

Huang, C., Ji, X., Zhou, W., Huang, Z., Peng, X., Fan, L., Lin, G., & Zhu, W. (2020). Coronavirus: A possible cause of reduced male fertility. Andrology., 9 (1), 80-87.

Illiano, E., Trama, F., & Constantini, E. (2020). Could COVID-19 have an impact on male fertility?. J. Andrology., 52 (6), e13654.

Khalili, M. A., Leisegang, K., Majzoub, A., Finelli, R., Selvam, M. K., Henkel, R., Mojgan, M., & Agarwal, A. (2020). Male Fertility and the COVID-19 Pandemic: Systematic Review of the Literature. World J Mens Health., 38 (4), 506-520.

Kumar, A., Singh, R., Kaur, J., Pandey, S., Sharma, V., Thakur, L., Sati, S., Mani, S., Asthana, S., Sharma, T. K., Chaudhuri, S., Bhattacharyya, S., & Kumar, N. (2021). Wuhan to World: The COVID-19 Pandemic. Front Cell Infect Microbiol., 11, e596201.

Leal, M. C., Pinheiro, S. V., Ferreira, A. J., Santos, S. A., Bordoni, L. S., Alenina, N., Bader, M., & Franla, L. R. (2009). The role of angiotensin-(1–7) receptor Mas in spermatogenesis in mice and rats. Journal of Anatomy., 214 (5), 736-743.

Li, H., Xiao, X., Zhang, J., Zafar, M. I., Wu, C., Long, Y., Lu, W., Pan, F., Meng, T., Zhao, K., Zhou, L., Shen, S., Liu, L., Liu, Q., & Xiong, C. (2020). Impaired spermatogenesis in COVID-19 patients. E Clin. Med., 28, 100604.

Li, D., Jin, M., Bao, P., Zhao, W., & Zhang, S. (2020) Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease 2019. JAMA Netw Open., 3 (5), e208292.

Ling, Y., Xu, S., Lin, Y., Tian, D., Zhu, Z., Dai, F., Wu, F., Song, Z., Huang, W., Chen, J., Hu, B., Wang, S., Mao, E., Zhu, L., Zhang, W., & Lu, H. (2020). Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients. Chin Med J (Engl)., 133 (9), 1039-1043.

Ma L, Xie W, Li D, Shi L, Mao Y, Xiong Y, Zhang, Y., & Zhang, M. (2020). Effect of SARS-CoV-2 infection upon male gonadal function: A single center-based study. MedRxiv.

Mannur, S., Jabeen, T., Khader, M. A., & Rao, L. S. (2021). Post-COVID-19-associated decline in long-term male fertility and embryo quality during assisted reproductive technology. QJM., 114 (5), 328-330.

Meng, T. T., Dong, R. J., & Li, T. G. (2021). Relationship between COVID-19 and the male reproductive system. Eur Rev Med Pharmacol Sci., 25, 1109-1113.

Navarra, A., Albani, E., Castellano, S., Arruzzolo, R., & Levi-Setti, P. E. (2020). Coronavirus Disease-19 Infection: Implications on Male Fertility and Reproduction. Front. Physiol., 11, 574761.

Oliveira, B. A., Oliveira, L. C. Sabino, E. C, & Okay, T. S. (2020). SARS-CoV-2 and the COVID-19 disease: a mini review on diagnostic methods. Rev. Inst. Med. trop. S. Paulo., 62, e44.

Pan, F., Xiao, X., Guo, J., Sing, Y., Li, H., Patel, D. P., Spivak, A. M., Alukal, J. P., Zhang, X., Xiong, C., Li, P. S., & Hotaling, J. M. (2020). No evidence of SARS-CoV-2 in semen of males recovering from COVID-19. Fertility and Sterility., 113 (6), 1135-1139.

Paoli, D., Pallotti, F., Colangelo, S., Basilico, F., Mazzuti, L., Turriziani, O., Antonelli, G., Lenzi, A., & Lombardo, F. (2020). Study of SARS-CoV-2 in semen and urine samples of a volunteer with positive naso-pharyngeal swab. J. Endoc. Invest., 43, 1819-1822.

Pascolo, L., Zito, G., Zupin, L., Luppi, S., Giolo, E., Martinelli, M., Rocco D. D., Crovella, S., & Ricci, G. (2020). Renin Angiotensin System, COVID-19 and Male Fertility: Any Risk for Conceiving? Microorganisms., 8 (10), 1492.

Pereira, A. S., Shitsuka, D. M., Parreira, F. J., & Shitsuka, R. (2018). Methodology of scientific research. [e-Book]. Santa Maria City. UAB / NTE / UFSM Editors. Accessed on: May, 1st, 2022. Available https://repositorio.ufsm.br/bitstream/handle/1/15824/Lic_Computacao_Metodologia-Pesquisa-Cientifica.pdf?sequence=1

Prestes, T. R., Rocha, N. P., Miranda, A. S., Teixeira, A. L., & Silva, A. C.(2017). The Anti-Inflammatory Potential of ACE2/Angiotensin-(1-7)/Mas Receptor Axis: Evidence from Basic and Clinical Research. Curr Drug Targets., 18 (11), 1301-1313.

Qiao, Y., Wang, X. M., Mannan, R., Pitchiaya, S., Zhang, Y., Wotring, J. W., Xiao, L., Robinson, D. R., Wu, Y., Tien, J. C., Cao, X., Simko, S. A., Apel, I. J., Bawa, P., Kregel, S., Narayanan, S. P., Raskind, G., Ellison, S. J., Parolia, A., Zelenka-Wang, S., McMurry, L., Su, F., Wang, R., Cheng, Y., Delekta, A. D., Mei, Z., Pretto, C. D., Wang, S., Mehra, R., Sexton, J. Z., & Chinnayan, A. M. (2020). Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2. Proceedings of the National Academy of Sciences., 118 (1), e2021450118.

Quan, W., Chen, J., Liu, Z., Tian, J., Chen, X., Wu, T., Ji, Z., Tang, J., Chu, H., Xu, H., Zhao, Y., & Zheng, Q. (2020). No SARS-CoV-2 in expressed prostatic secretion of patients with coronavirus disease 2019: a descriptive multicentre study in China. MedRxiv.

Reis, A. B., Araújo, F. C., Pereira, V. M., Reis, A. M., Santos, R. A., & Reis, F. M. (2010). Angiotensin (1-7) and its receptor Mas are expressed in the human testis: implications for male infertility. J. Mol. Histol., 41, 75-80.

Rojas, H., Ritter, C., & Pizzol, F. D. (2011). Mecanismos de disfunção da barreira hematoencefálica no paciente criticamente enfermo: ênfase no papel das metaloproteinases de matriz. Rev. bras. ter. intensiva, 23 (2).

Schroeder, M., Schaumburg, B., Mueller, Z., Parplys, A., Jarczak, D., Nierhaus, A., Kloetgen, A., Schneider, B., Peschka, M., Stoll, F., Bai, T., Jacobsen, H., Zickler, M., Stanelle-Bertram, S., Heer, G., Renné, T., Meinhardt, A., Heeren, J., Aberle, J., McHardy, A. C., Schluter, H., Hiller, J., Peine, S., Kreienbrock, L., Klingel, K., Kluge, S., & Gabriel, G. (2020). Sex hormone and metabolic dysregulations are associated with critical illness in male Covid-19 patients. Emerging Microbes & Infections., 10 (1).

Seymen, C. M. (2020). The other side of COVID19 pandemic:Effects on male fertility. J. Med. Virology., 93 (3), 1396-1402.

Shen, Q., Xiao, X., Aierken, A., Yue, W., Wu, X., Liao, M., & Hua, J. (2020). The ACE2 expression in Sertoli cells and germ cells may cause male reproductive disorder after SARS-CoV-2 infection. J Cell Mol Med., 24 (16), 9472-9477.

Song, C., Wang, Y., Li, W., Hu, B., Chen, G., Xia, P., Wang, W., Li, C., Hu, Z., Yang, X., Yao, B., & Liu, Y. (2020). Detection of 2019 novel coronavirus in semen and testicular biopsy specimen of COVID-19 patients. MedRxiv.

Stelzig, K. E., Canepa-Escaro, F., Schiliro, M., Berdnikovs, S., Prakash, Y. S., & Chiarella, S. E. (2020). Estrogen regulates the expression of SARS-CoV-2 receptor ACE2 in differentiated airway epithelial cells. Amer. Journ. of Physiol., 318 (6), 1280-1281.

Sun, J. (2020). The hypothesis that SARS-CoV-2 affects male reproductive ability by regulating autophagy. Elsevier., 143.

Veldhuis, J., Yang, R., Roelfsema, R., & Takahashi, P. (2016). Proinflammatory Cytokine Infusion Attenuates LH's Feedforward on Testosterone Secretion: Modulation by Age. J Clin Endocrinol Metab., 101 (2), 539-549.

Vishvkarma, R., & Rajender, S. (2020). Could SARS-CoV-2 affect male fertility?. Andrology., 52 (9), e13712.

World Heatlh Organization. (WHO). (2021). Coronavirus (COVID-19) Dashboard. https://covid19.who.int/ .

Xu, J., Qi, L., Chi, X., Yang, J., Wei, X., Gong, E., Peh, S., & Gu, J. (2006). Orchitis: a complication of severe acute respiratory syndrome (SARS). Biol Reprod., 74 (2), 410-416.

Yang, M., Chen, S., Huang, B., Zhong, J., Su, H., Chen, Y., Cao, Q., Ma, L., He, J., Li, X., Li, X., Zhou, J., Fan, J., Luo, D., Chang, X., Arkun, K., Zhou, M., & Nie, X. (2020). Pathological Findings in the Testes of COVID-19 Patients: Clinical Implications. Eur. Urol. Focus., 6 (5), 1124-1129.

Younis, J. S., Abassi, Z., & Skorecki, K. (2020). Is there an impact of the COVID-19 pandemic on male fertility? The ACE2 connection. Am J Physiol Endocrinol Metab., 318 (6), 878-880.

Zhao, M. M., Yang, W. L., Yang, F., Zhang, L., Huang, W., Hou, W., Fan, C., Jin, R., Feng, Y., Wang, Y., & Yang, J. (2021). Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development. Sig Transduct Target Ther., 6 (1), 134.

Downloads

Published

06/07/2022

How to Cite

CARVALHO, M. dos S. do N. .; CARVALHO, M. do N.; LIMA, J. C. de; SILVA, J. C.; CABRAL, A. B. Male reproductive system alterations by SARS-CoV-2 and its pathophysiology: A review. Research, Society and Development, [S. l.], v. 11, n. 9, p. e17211931727, 2022. DOI: 10.33448/rsd-v11i9.31727. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/31727. Acesso em: 22 dec. 2024.

Issue

Section

Health Sciences