Hostname: page-component-8448b6f56d-m8qmq Total loading time: 0 Render date: 2024-04-23T17:33:09.990Z Has data issue: false hasContentIssue false
  • English
  • Français

Review of Sertoli cell dysfunction caused by COVID-19 that could affect male fertility

Published online by Cambridge University Press:  28 June 2021

Amirreza Niazi Tabar ,
Kiana Sojoudi ,
Hannaneh Henduei  and
Hossein Azizi Open the ORCID record for Hossein Azizi [Opens in a new window]
Amirreza Niazi Tabar*
Affiliation:
Faculty of Biotechnology, Amol University of Special Modern Technologies, Amol, Iran
Kiana Sojoudi
Affiliation:
Faculty of Biotechnology, Amol University of Special Modern Technologies, Amol, Iran
Hannaneh Henduei
Affiliation:
Faculty of Biotechnology, Amol University of Special Modern Technologies, Amol, Iran
Hossein Azizi
Affiliation:
Faculty of Biotechnology, Amol University of Special Modern Technologies, Amol, Iran
*
Author for correspondence: Amirreza Niazi Tabar. Faculty of Biotechnology, Amol University of Special Modern Technologies, Amol, Iran. Email: A.niazitabar@ausmt.ac.ir
Get access Rights & Permissions [Opens in a new window]

Abstract

Spermatogenesis is a complex and elaborate differentiation process and is vital for male fertility. Sertoli cells play a major role in fertility and induce spermatogenesis by protecting, nourishing, and supporting germ cells. It has been speculated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could directly affect the male reproductive system, and therefore heredity and fertility. The similarity of SARS-CoV-2 to SARS-CoV could confirm this hypothesis because both viruses use angiotensin-converting enzyme (ACE2) as the receptor to enter human cells. ACE2 is expressed by Sertoli cells and other testicular cells, therefore COVID-19 has the potential to impair fertility by destroying Sertoli cells. This hypothesis should be evaluated and confirmed by monitoring fertility in patients with COVID-19.

Keywords

COVID-19Germ cellsMale fertilitySARS coronavirusesSertoli cells
Type
Review Article
Information
Zygote , Volume 30 , Issue 1 , February 2022 , pp. 17 - 24
Copyright
© The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abobaker, A and Raba, AA (2021). Does COVID-19 affect male fertility? World J Urol 39, 975–6.CrossRefGoogle ScholarPubMed
Almeida, RDN, Braz-de-Melo, HA, Santos, IO, Corrêa, R, Kobinger, GP and Magalhaes, KG (2020). The cellular impact of the ZIKA virus on male reproductive tract immunology and physiology. Cells 9, 1006.CrossRefGoogle ScholarPubMed
Archana, SS, Selvaraju, S, Binsila, BK, Arangasamy, A and Krawetz, SA (2019). Immune regulatory molecules as modifiers of semen and fertility: A review. Mol Reprod Dev 86, 1485–504.CrossRefGoogle ScholarPubMed
Atkinson, B, Thorburn, F, Petridou, C, Bailey, D, Hewson, R, Simpson, AJ, Brooks, TJ and Aarons, EJ (2017). Presence and persistence of Zika virus RNA in semen, United Kingdom, 2016. Emerg Infect Dis 23, 611–5.CrossRefGoogle ScholarPubMed
Azizi, H, Niazi Tabar, A and Mohammadi, A (2020). Experimental investigation of Ki67, POU5F1, and ZBTB16 expression in the pig and mouse testicular cells using immunocytochemistry and RT-PCR. SJIMU 28, 1–10.CrossRefGoogle Scholar
Azizi, H, Niazi Tabar, A, Mohammadi, A and Skutella, T (2021). Characterization of DDX4 gene expression in human cases with non-obstructive azoospermia and in sterile and fertile mice. J Reprod Infertil 22, 85–91.Google ScholarPubMed
Babushkina, EA, Belokopytova, LV, Grachev, AM, Meko, DM and Vaganov, EA (2017). Variation of the hydrological regime of Bele-Shira closed basin in Southern Siberia and its reflection in the radial growth of Larix sibirica . Reg Environ Change 17, 1725–37.CrossRefGoogle Scholar
Baker, PJ and O’Shaughnessy, PJ (2001). Role of gonadotrophins in regulating numbers of Leydig and Sertoli cells during fetal and postnatal development in mice. Reproduction 122, 227–34.CrossRefGoogle ScholarPubMed
Berger, T and Nitta-Oda, BJ (2018). Increased testicular estradiol during the neonatal interval reduces Sertoli cell numbers. Anim Reprod Sci 189, 146–51.CrossRefGoogle ScholarPubMed
CDC COVID-19 Response Team (2020). Severe outcomes among patients with coronavirus disease 2019 (COVID-19)—United States, February 12–March 16, 2020. MMWR 69, 343–6.CrossRefGoogle Scholar
Chan, JF, Yuan, S, Kok, KH, To, KK, Chu, H, Yang, J, Xing, F, Liu, J, Yip, CC, Poon, RW, Tsoi, HW, Lo, SK, Chan, KH, Poon, VK, Chan, WM, Ip, JD, Cai, JP, Cheng, VC, Chen, H, Hui, CK and Yuen, KY (2020). A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 395, 514–23.CrossRefGoogle ScholarPubMed
Chen, SR and Liu, YX (2015). Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling. Reproduction 149, R159–67.CrossRefGoogle ScholarPubMed
Chen, Y, Zhou, Y, Wang, X, Qian, W and Han, X (2013). Microcystin-LR induces autophagy and apoptosis in rat Sertoli cells in vitro . Toxicon 76, 84–93.CrossRefGoogle ScholarPubMed
Chen, Y, Liu, Q and Guo, D (2020). Emerging coronaviruses: Genome structure, replication, and pathogenesis. J Med Virol 92, 418–23.CrossRefGoogle ScholarPubMed
Cheng, CY and Mruk, DD (2012). The blood–testis barrier and its implications for male contraception. Pharmacol Rev 64, 16–64.CrossRefGoogle ScholarPubMed
Chojnacka, K, Zarzycka, M and Mruk, DD (2016). Biology of the Sertoli cell in the fetal, pubertal, and adult mammalian testis. In: Piprek R (ed.) Molecular Mechanisms of Cell Differentiation in Gonad Development. Results and Problems in Cell Differentiation, vol 58, pp. 225–51. Springer, Cham.CrossRefGoogle Scholar
Crespillo-Andujar, C, Díaz-Menéndez, M and Mora-Rillo, M (2018). Evidence for previously unidentified sexual transmission of protozoan parasites. Emerg Infect Dis 24, 602–3.CrossRefGoogle ScholarPubMed
Crisóstomo, L, Alves, MG, Gorga, A, Sousa, M, Riera, MF, Galardo, MN, Meroni, SB and Oliveira, PF (2018) Molecular mechanisms and signaling pathways involved in the nutritional support of spermatogenesis by Sertoli cells. In: Alves, M and Oliveira, P (eds) Sertoli Cells. Methods in Molecular Biology, vol. 1748, pp. 129–55. Humana Press, New York, NY.CrossRefGoogle Scholar
Dimitrov, DS (2003). The secret life of ACE2 as a receptor for the SARS virus. Cell, 115, 652–3.CrossRefGoogle ScholarPubMed
Dutta, S and Sengupta, P (2021). SARS-CoV-2 and male infertility: Possible multifaceted pathology. Reprod Sci 28, 23–6.CrossRefGoogle ScholarPubMed
Fan, C, Li, K, Ding, Y and Lu, W (2020). ACE2 expression in kidney and testis may cause kidney and testis damage after 2019-nCoV infection. MedRxiv doi: https://doi.org/10.1101/2020.02.12.20022418 CrossRefGoogle Scholar
França, LR, Hess, RA, Dufour, JM, Hofmann, MC and Griswold, MD (2016). The Sertoli cell: one hundred fifty years of beauty and plasticity. Andrology, 4, 189–212.CrossRefGoogle ScholarPubMed
Gautam, P, Rao, M, Gothwal, M, Garg, PK and Bhattacharya, S (2019). Sertoli–Leydig cell tumor of ovary: a rare case report with heterologous elements and focal marked anaplasia. Int J Appl Basic Med Res 9, 62–4.Google ScholarPubMed
Griswold, MD (1995). Interactions between germ cells and Sertoli cells in the testis. Biol Reprod 52, 211–6.CrossRefGoogle ScholarPubMed
Griswold, MD (2018). 50 years of spermatogenesis: Sertoli cells and their interactions with germ cells. Biol Reprod 99, 87–100.CrossRefGoogle ScholarPubMed
Guma, FC, Wagner, M, Martini, LH and Bernard, EA (1997). Effect of FSH and insulin on lipogenesis in cultures of Sertoli cells from immature rats. Braz J Med Biol Res 30, 591–7.CrossRefGoogle ScholarPubMed
Gurung, P and Jialal, I (2020). Physiology, male reproductive system. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538429/ Google Scholar
Hedger, MP and Meinhardt, A (2003). Cytokines and the immune-testicular axis. J Reprod Immunol 58, 1–26.CrossRefGoogle ScholarPubMed
Hikmet, F, Méar, L, Edvinsson, Å Micke, P, Uhlén, M and Lindskog, C (2020). The protein expression profile of ACE2 in human tissues. Mol System Biol 16, e9610.CrossRefGoogle ScholarPubMed
Hoffmann, M, Kleine-Weber, H, Schroeder, S, Krüger, N, Herrler, T, Erichsen, S, Schiergens, TS, Herrler, G, Wu, NH, Nitsche, A, Müller, MA, Drosten, C and Pöhlmann, S (2020). SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181, 271–80.e8.CrossRefGoogle ScholarPubMed
Huang, C, Ji, X, Zhou, W, Huang, Z, Peng, X, Fan, L, Lin, G and Zhu, W (2021). Coronavirus: a possible cause of reduced male fertility. Andrology 9, 80–7.CrossRefGoogle ScholarPubMed
Illiano, E, Trama, F and Costantini, E (2020). Could COVID-19 have an impact on male fertility? Andrologia 52, e13654.CrossRefGoogle ScholarPubMed
Jia, H (2016). Pulmonary angiotensin-converting enzyme 2 (ACE2) and inflammatory lung disease. Shock 46, 239–48.CrossRefGoogle ScholarPubMed
Johnson, L, Thompson, DL and Varner, DD (2008). Role of Sertoli cell number and function on regulation of spermatogenesis. Anim Reprod Sci 105(1–2), 23–51.CrossRefGoogle ScholarPubMed
Karnik, SS, Unal, H, Kemp, JR, Tirupula, KC, Eguchi, S, Vanderheyden, PM and Thomas, WG (2015). International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin receptors: Interpreters of pathophysiological angiotensinergic stimuli [corrected]. Pharmacol Rev 67, 754–819.CrossRefGoogle Scholar
Kearney, J (2020). Chloroquine as a potential treatment and prevention measure for the 2019 novel coronavirus: A review. Available from: 10.20944/preprints202003.0275.v1CrossRefGoogle Scholar
Kissler, SM, Tedijanto, C, Goldstein, E, Grad, YH and Lipsitch, M (2020) Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period. Science 368(6493), 860–8.CrossRefGoogle ScholarPubMed
Lai, CC, Shih, TP, Ko, WC, Tang, HJ and Hsueh, PR (2020). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges. Int J Antimicrob Agents 55, 105924.CrossRefGoogle ScholarPubMed
Liu, X, Chen, Y, Tang, W, Zhang, L, Chen, W, Yan, Z, Yuan, P, Yang, M, Kong, S, Yan, L, Qiao, J (2020). 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 63, 1006–15.CrossRefGoogle ScholarPubMed
Lu, R, Zhao, X, Li, J, Niu, P, Yang, B, Wu, H, Wang, W, Song, H, Huang, B, Zhu, N, Bi, Y, Ma, X, Zhan, F, Wang, L, Hu, T, Zhou, H, Hu, Z, Zhou, W, Zhao, L, Chen, J, Meng, Y, Wang, J, Lin, Y, Yuan, J, Xie, Z, Ma, J, Liu, WJ, Wang, D, Xu, W, Holmes, EC, Gao, GF, Wu, G, Chen, W, Shi, W and Tan, W (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 395(10224), 565–74.CrossRefGoogle ScholarPubMed
Ma, L, Xie, W, Li, D, Shi, L, Mao, Y, Xiong, Y, Zhang, Y and Zhang, M (2020). Effect of SARS-CoV-2 infection upon male gonadal function: A single center-based study. MedRxiv doi: https://doi.org/10.1101/2020.03.21.20037267 Google Scholar
Marconi, M and Weidner, W (2017). Site and risk factors of antisperm antibodies production in the male population. In: Krause, WKH and Naz, RK (eds). Immune Infertility: Impact of Immune Reactions on Human Fertility, 2nd Edition, pp. 133–147. Berlin: Springer.CrossRefGoogle Scholar
Mikuz, G (2019). Die multitasking-Sertoli-Zelle. Pathologe 40(S3), 318–24.CrossRefGoogle Scholar
Millet, JK and Whittaker, GR (2018). Physiological and molecular triggers for SARS-CoV membrane fusion and entry into host cells. Virology 517, 3–8.CrossRefGoogle ScholarPubMed
Oliveira, PF and Alves, MG (2015). Sertoli cell metabolism and spermatogenesis. Springer.CrossRefGoogle ScholarPubMed
Ou, X, Liu, Y, Lei, X, Li, P, Mi, D, Ren, L, Guo, L, Guo, R, Chen, T, Hu, J, Xiang, Z, Mu, Z, Chen, X, Chen, J, Hu, K, Jin, Q, Wang, J and Qian, Z (2020). Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 11, 1620.CrossRefGoogle ScholarPubMed
Petersen, C and Söder, O (2006). The Sertoli cell – a hormonal target and ʼsuper’ nurse for germ cells that determines testicular size. Horm Res 66, 153–61.Google ScholarPubMed
Puggioni, G, Pintus, D, Melzi, E, Meloni, G, Rocchigiani, AM, Maestrale, C, Manunta, D, Savini, G, Dattena, M, Oggiano, A, Palmarini, M and Ligios, C (2018). Testicular degeneration and infertility following arbovirus infection. J Virol 92, e01131–18.CrossRefGoogle ScholarPubMed
Qu, N, Ogawa, Y, Kuramasu, M, Nagahori, K, Sakabe, K and Itoh, M (2020). Immunological microenvironment in the testis. Reprod Med Biol 19, 24–31.CrossRefGoogle ScholarPubMed
Ragab, D, Salah Eldin, H, Taeimah, M, Khattab, R and Salem, R (2020). The COVID-19 cytokine storm; what we know so far. Front Immunol 11, 1446.CrossRefGoogle ScholarPubMed
Rato, L, Alves, MG, Socorro, S, Duarte, AI, Cavaco, JE and Oliveira, PF (2012). Metabolic regulation is important for spermatogenesis. Nat Rev Urol 9, 330–8.CrossRefGoogle ScholarPubMed
Rebourcet, D, Darbey, A, Monteiro, A, Soffientini, U, Tsai, YT, Handel, I, Pitetti, JL, Nef, S, Smith, LB and O’Shaughnessy, PJ (2017). Sertoli cell number defines and predicts germ and Leydig cell population sizes in the adult mouse testis. Endocrinology 158, 2955–69.CrossRefGoogle ScholarPubMed
Ritzén, EM (1983). Chemical messengers between Sertoli cells and neighbouring cells. J Steroid Biochem 19(1B), 499–504.CrossRefGoogle ScholarPubMed
Shen, Q, Xiao, X, Aierken, A, Yue, W, Wu, X, Liao, M and 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, 9472–7.CrossRefGoogle ScholarPubMed
Shi, JF, Li, YK, Ren, K, Xie, YJ, Yin, WD and Mo, ZC (2018). Characterization of cholesterol metabolism in Sertoli cells and spermatogenesis. Mol Med Rep 17, 705–13.Google ScholarPubMed
Siemann, DN, Strange, DP, Maharaj, PN, Shi, PY and Verma, S (2017). Zika virus infects human Sertoli cells and modulates the integrity of the in vitro blood–testis barrier model. J Virol 91, e00623–17.CrossRefGoogle ScholarPubMed
Singh, R, Hamada, AJ and Agarwal, A (2011). Thyroid hormones in male reproduction and fertility. Open Reprod Sci J 3, 98–104.Google Scholar
Steinberger, A, Heindel, JJ, Lindsey, JN, Elkington, JS, Sanborn, BM and Steinberger, E (1975). Isolation and culture of FSH responsive Sertoli cells. Endocr Res Commun 2, 261–72.CrossRefGoogle ScholarPubMed
Tarulli, GA, Stanton, PG and Meachem, SJ (2012). Is the adult Sertoli cell terminally differentiated? Biol Reprod 87, 13, 1–11.CrossRefGoogle ScholarPubMed
Tindall, DJ, Rowley, DR, Murthy, L, Lipshultz, LI and Chang, CH (1985). Structure and biochemistry of the Sertoli cell. Int Rev Cytol 94, 127–49.CrossRefGoogle ScholarPubMed
Turner, AJ (2015). ACE2 cell biology, regulation, and physiological functions. In: Unger, T, Steckelings, UM and Souza dos Santos, R (eds), The Protective Arm of the Renin Angiotensin System (RAS), pp. 185–9. Elsevier CrossRefGoogle Scholar
Vishvkarma, R and Rajender, S (2020). Could SARS-CoV-2 affect male fertility? Andrologia 52, e13712.CrossRefGoogle ScholarPubMed
Vogl, W, Lyon, K, Adams, A, Piva, M and Nassour, V (2018). The endoplasmic reticulum, calcium signaling and junction turnover in Sertoli cells. Reproduction 155, R93–104.Google ScholarPubMed
Walker, WH (2003). Nongenomic actions of androgen in Sertoli cells. Curr Top Dev Biol 56, 25–53.CrossRefGoogle ScholarPubMed
Walls, AC, Park, YJ, Tortorici, MA, Wall, A, McGuire, AT and Veesler, D (2020). Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181, 281–92.e6.CrossRefGoogle ScholarPubMed
Wang, H, Wen, L, Yuan, Q, Sun, M, Niu, M and He, Z (2016). Establishment and applications of male germ cell and Sertoli cell lines. Reproduction 152, R31–40.CrossRefGoogle Scholar
Wang, Z and Xu, X (2020). 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 9, 920.CrossRefGoogle ScholarPubMed
Xu, J, Qi, L, Chi, X, Yang, J, Wei, X, Gong, E, Peh, S and Gu, J (2006). Orchitis: a complication of severe acute respiratory syndrome (SARS). Biol Reprod 74, 410–6.CrossRefGoogle Scholar
Yang, M, Chen, S, Huang, B, Zhong, JM, Su, H, Chen, YJ, Cao, Q, Ma, L, He, J, Li, XF, Li, X, Zhou, JJ, Fan, J, Luo, DJ, Chang, XN, Arkun, K, Zhou, M and Nie, X (2020). Pathological findings in the testes of COVID-19 patients: clinical implications. Eur Urol Focus 6, 1124–9.CrossRefGoogle ScholarPubMed
Yefimova, MG, Messaddeq, N, Harnois, T, Meunier, AC, Clarhaut, J, Noblanc, A, Weickert, JL, Cantereau, A, Philippe, M, Bourmeyster, N and Benzakour, O (2013). A chimerical phagocytosis model reveals the recruitment by Sertoli cells of autophagy for the degradation of ingested illegitimate substrates. Autophagy 9, 653–66.CrossRefGoogle ScholarPubMed
Younis, JS, Abassi, Z and Skorecki, K (2020). Is there an impact of the COVID-19 pandemic on male fertility? The ACE2 connection. Am J Physiol Endocrinol Metab 318, E878–80.CrossRefGoogle ScholarPubMed
Zhou, L, Niu, Z, Jiang, X, Zhang, Z, Zheng, Y, Wang, Z, Zhu, Y, Gao, L, Huang, H, Wang, X and Sun, Q (2020). SARS-CoV-2 targets by the pscRNA profiling of ACE2, TMPRSS2 and Furin proteases. iScience 23, 101744.CrossRefGoogle ScholarPubMed