Generic placeholder image

Coronaviruses

Editor-in-Chief

ISSN (Print): 2666-7967
ISSN (Online): 2666-7975

Review Article

Immune-endocrine Interactions and Remodelling of Testicular Cells’ Metabolic Homeostasis During SARS-CoV-2 Infection

Author(s): Suvendu Ghosh, Partha Sarathi Singha and Debosree Ghosh*

Volume 5, Issue 4, 2024

Published on: 24 January, 2024

Article ID: e240124226149 Pages: 8

DOI: 10.2174/0126667975267329231212043556

Price: $65

Open Access Journals Promotions 2
conference banner
Abstract

The testis is the site for the production of sperm and testosterone. There exists a natural blood-testis barrier in order to maintain the internal metabolic homeostasis of the male gonads. Variation in metabolic homeostasis may lead to unexplained fertility issues, reduced production of sperm, production of deformed, non-viable sperm, and hamper the production of testosterone during SARSCoV- 2 infection along with physiological systems of the human body in different situations. The male reproductive system than female is more adversely affected by the immune changes due to viral infection. There occurs a significant immune–endocrine interaction in the gonads, which can be more precisely termed an “immune-neuroendocrine interaction”. The “hypothalamus-pituitary-gonadal axis” plays an important role in maintaining the normal metabolic homeostasis of the testis. The net impact is a change and reordering of the testicular metabolic homeostasis, leading to compromised male infertility in post-COVID-19 infected individuals. This review is a brief account of the immune and endocrine interactions that occur in the testis during COVID-19 infection, leading to remodeling of the testicular metabolic homeostasis by various mechanisms, which ultimately may lead to infertility in individuals who have been infected by the Coronavirus.

Keywords: COVID-19, homeostasis, hypothalamus-pituitary-gonadal axis, infertility, immune-neuroendocrine interaction, testis.

Graphical Abstract
[1]
Ghosh S, Ghosh D. Current perspectives of male infertility induced by immunomodulation due to reproductive tract infections: A mini review. Chem Biol Lett 2020; 7(2): 85-91.
[2]
Gong J, Zeng Q, Yu D, Duan YG. T lymphocytes and testicular immunity: A new insight into immune regulation in testes. Int J Mol Sci 2020; 22(1): 57.
[http://dx.doi.org/10.3390/ijms22010057] [PMID: 33374605]
[3]
Jacobo P, Guazzone VA, Jarazo-Dietrich S, Theas MS, Lustig L. Differential changes in CD4+ and CD8+ effector and regulatory T lymphocyte subsets in the testis of rats undergoing autoimmune orchitis. J Reprod Immunol 2009; 81(1): 44-54.
[http://dx.doi.org/10.1016/j.jri.2009.04.005] [PMID: 19520436]
[4]
Bhushan S, Theas MS, Guazzone VA, et al. Immune cell subtypes and their function in the testis. Front Immunol 2020; 11: 583304.
[http://dx.doi.org/10.3389/fimmu.2020.583304] [PMID: 33101311]
[5]
Guazzone VA, Jacobo P, Theas MS, Lustig L. Cytokines and chemokines in testicular inflammation: A brief review. Microsc Res Tech 2009; 72(8): 620-8.
[http://dx.doi.org/10.1002/jemt.20704] [PMID: 19263422]
[6]
Fijak M, Pilatz A, Hedger MP, et al. Infectious, inflammatory and ‘autoimmune’ male factor infertility: How do rodent models inform clinical practice? Hum Reprod Update 2018; 24(4): 416-41.
[http://dx.doi.org/10.1093/humupd/dmy009] [PMID: 29648649]
[7]
Cicco S, Cicco G, Racanelli V, Vacca A. Neutrophil extracellular traps (NETs) and damage-associated molecular patterns (DAMPs): Two potential targets for COVID-19 treatment. Mediators Inflamm 2020; 2020: 1-25.
[http://dx.doi.org/10.1155/2020/7527953] [PMID: 32724296]
[8]
Al-Benna S. Angiotensin-converting enzyme 2 gene expression in human male urological tissues: implications for pathogenesis and virus transmission pathways. Afr J Urol 2021; 27(1): 89.
[http://dx.doi.org/10.1186/s12301-021-00192-4] [PMID: 34230799]
[9]
Li H, Xiao X, Zhang J, et al. Impaired spermatogenesis in COVID-19 patients. EClinicalMedicine 2020; 28: 100604.
[http://dx.doi.org/10.1016/j.eclinm.2020.100604] [PMID: 33134901]
[10]
Sharun K, Tiwari R, Dhama K. SARS-CoV-2 in semen: Potential for sexual transmission in COVID-19. Int J Surg 2020; 84: 156-8.
[http://dx.doi.org/10.1016/j.ijsu.2020.11.011] [PMID: 33197596]
[11]
Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med 2020; 76: 14-20.
[http://dx.doi.org/10.1016/j.ejim.2020.04.037] [PMID: 32336612]
[12]
Souyris M, Mejía JE, Chaumeil J, Guéry JC. Female predisposition to TLR7-driven autoimmunity: Gene dosage and the escape from X chromosome inactivation. Semin Immunopathol 2019; 41(2): 153-64.
[http://dx.doi.org/10.1007/s00281-018-0712-y] [PMID: 30276444]
[13]
Pagliaro P, Penna C. ACE/ACE2 Ratio: A key also in 2019 coronavirus disease (COVID-19)? Front Med 2020; 7: 335.
[http://dx.doi.org/10.3389/fmed.2020.00335] [PMID: 32626721]
[14]
Alrefaie Z, Alsufyani HA. Renin–Angiotensin system implications to COVID-19 comorbidities. J Microsc Ultrastruct 2020; 8(4): 148-51.
[http://dx.doi.org/10.4103/jmau.jmau_105_20] [PMID: 33623738]
[15]
Shi W, Lv J, Lin L. Coagulopathy in COVID-19: Focus on vascular thrombotic events. J Mol Cell Cardiol 2020; 146: 32-40.
[http://dx.doi.org/10.1016/j.yjmcc.2020.07.003] [PMID: 32681845]
[16]
Cano RLE, Lopera HDE. Introduction to T and B lymphocytes. Autoimmunity: From Bench to Bedside. Bogota, Colombia: El Rosario University Press 2018.
[17]
Alberts B, Johnson A, Lewis J, et al. Molecular biology of the cell. 4th edition. In: Helper T Cells and Lymphocyte Activation. New York: Garland Science 2002.
[18]
Lucas JM, True L, Hawley S, et al. The androgen‐regulated type II serine protease TMPRSS2 is differentially expressed and mislocalized in prostate adenocarcinoma. J Pathol 2008; 215(2): 118-25.
[http://dx.doi.org/10.1002/path.2330] [PMID: 18338334]
[19]
Gilbert SF. Developmental biology. In: Sinauer Associates. Sunderland 2000.
[20]
Illiano E, Trama F, Costantini E. Could COVID‐19 have an impact on male fertility? Andrologia 2020; 52(6): e13654.
[http://dx.doi.org/10.1111/and.13654] [PMID: 32436229]
[21]
Cheng CY, Mruk DD. The blood-testis barrier and its implications for male contraception. Pharmacol Rev 2012; 64(1): 16-64.
[http://dx.doi.org/10.1124/pr.110.002790] [PMID: 22039149]
[22]
Sharma GT, Chandra V, Mankuzhy P, et al. Physiological implications of COVID-19 in reproduction: Angiotensin-converting enzyme 2 a key player. Reprod Fertil Dev 2021; 33(6): 381-91.
[http://dx.doi.org/10.1071/RD20274] [PMID: 33731252]
[23]
Khalili MA, Leisegang K, Majzoub A, et al. Male Fertility and the COVID-19 Pandemic: Systematic review of the literature. World J Mens Health 2020; 38(4): 506-20.
[http://dx.doi.org/10.5534/wjmh.200134] [PMID: 32814369]
[24]
Aronson PS. Ion exchangers mediating Na+, HCO3 - and Cl- transport in the renal proximal tubule. J Nephrol 2006; 19(9): S3-S10.
[PMID: 16736438]
[25]
Gervasi MG, Visconti PE. Molecular changes and signaling events occurring in spermatozoa during epididymal maturation. Andrology 2017; 5(2): 204-18.
[http://dx.doi.org/10.1111/andr.12320] [PMID: 28297559]
[26]
Alahmar A. Role of oxidative stress in male infertility: An updated review. J Hum Reprod Sci 2019; 12(1): 4-18.
[http://dx.doi.org/10.4103/jhrs.JHRS_150_18] [PMID: 31007461]
[27]
Nita M, Grzybowski A. The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults. Oxid Med Cell Longev 2016; 2016: 1-23.
[http://dx.doi.org/10.1155/2016/3164734] [PMID: 26881021]
[28]
Goulis DG, Tarlatzis BC. Metabolic syndrome and reproduction: I. Testicular function. Gynecol Endocrinol 2008; 24(1): 33-9.
[http://dx.doi.org/10.1080/09513590701582273] [PMID: 18224542]
[29]
Bansal R, Gubbi S, Muniyappa R. Metabolic syndrome and COVID 19: Endocrine-immune-vascular interactions shapes clinical course. Endocrinology 2020; 161(10): bqaa112.
[http://dx.doi.org/10.1210/endocr/bqaa112] [PMID: 32603424]
[30]
Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in italy. JAMA 2020; 323(18): 1775-6.
[http://dx.doi.org/10.1001/jama.2020.4683] [PMID: 32203977]
[31]
Crisóstomo L, Jarak I, Rato LP, et al. Inheritable testicular metabolic memory of high-fat diet causes transgenerational sperm defects in mice. Sci Rep 2021; 11(1): 9444.
[http://dx.doi.org/10.1038/s41598-021-88981-3] [PMID: 33941835]
[32]
Selvaraj K, Ravichandran S, Krishnan S, Radhakrishnan RK, Manickam N, Kandasamy M. Testicular atrophy and hypothalamic pathology in COVID-19: Possibility of the incidence of male infertility and HPG axis abnormalities. Reprod Sci 2021; 28(10): 2735-42.
[http://dx.doi.org/10.1007/s43032-020-00441-x] [PMID: 33415647]
[33]
Bu P, Yagi S, Shiota K, et al. Origin of a rapidly evolving homeostatic control system programming testis function. J Endocrinol 2017; 234(2): 217-32.
[http://dx.doi.org/10.1530/JOE-17-0250] [PMID: 28576872]
[34]
Sèdes L, Thirouard L, Maqdasy S, et al. Cholesterol: A gatekeeper of male fertility? Front Endocrinol 2018; 9: 369.
[http://dx.doi.org/10.3389/fendo.2018.00369] [PMID: 30072948]
[35]
Luís R, Marco A, Silvia S, Ana D, Jose C, Pedro O. Metabolic regulation is important for spermatogenesis. Nature reviews Urology 2012; 9: 330-8.
[http://dx.doi.org/10.1038/nrurol.2012.77]
[36]
Omolaoye TS, Jalaleddine N, Cardona Maya WD, du Plessis SS. Mechanisms of SARS-CoV-2 and male infertility: Could connexin and pannexin play a role? Front Physiol 2022; 13: 866675.
[http://dx.doi.org/10.3389/fphys.2022.866675] [PMID: 35721552]
[37]
Li X, Chen Z, Geng J, et al. COVID-19 and male reproduction: A thorny problem. Am J Men Health 2022; 16(1)
[http://dx.doi.org/10.1177/15579883221074816] [PMID: 35176914]
[38]
Ahmed R. Crosstalk between SARS-CoV-2 and testicular hemostasis: Perspective view. In: Agrawal M, Biswas S, Eds. Biotechnology to Combat COVID-19. London: IntechOpen 2021.
[http://dx.doi.org/10.5772/intechopen.98218]
[39]
Jiang L, Zheng T, Huang J, et al. Association of semen cytokines with reactive oxygen species and histone transition abnormalities. J Assist Reprod Genet 2016; 33(9): 1239-46.
[http://dx.doi.org/10.1007/s10815-016-0756-7] [PMID: 27364628]
[40]
Mathur PP, D’Cruz SC. The effect of environmental contaminants on testicular function. Asian J Androl 2011; 13(4): 585-91.
[http://dx.doi.org/10.1038/aja.2011.40] [PMID: 21706039]
[41]
Asadi N, Bahmani M, Kheradmand A, Rafieian-Kopaei M. The impact of oxidative stress on testicular function and the role of antioxidants in improving it: A review. J Clin Diagn Res 2017; 11(5): IE01-5.
[http://dx.doi.org/10.7860/JCDR/2017/23927.9886] [PMID: 28658802]
[42]
Adli A, Rahimi M, Khodaie R, Hashemzaei N, Hosseini SM. Role of genetic variants and host polymorphisms on COVID‐19: From viral entrance mechanisms to immunological reactions. J Med Virol 2022; 94(5): 1846-65.
[http://dx.doi.org/10.1002/jmv.27615] [PMID: 35076118]
[43]
Spiering AE, de Vries TJ. Why females do better: The X chromosomal TLR7 Gene-Dose Effect in COVID-19. Front Immunol 2021; 12: 756262.
[http://dx.doi.org/10.3389/fimmu.2021.756262] [PMID: 34858409]
[44]
Gemmati D, Bramanti B, Serino ML, Secchiero P, Zauli G, Tisato V. COVID-19 and individual genetic susceptibility/receptivity: Role of ACE1/ACE2 genes, immunity, inflammation and coagulation. might the double X-Chromosome in females be protective against SARS-CoV-2 compared to the single X-Chromosome in Males? Int J Mol Sci 2020; 21(10): 3474.
[http://dx.doi.org/10.3390/ijms21103474] [PMID: 32423094]
[45]
Available from: https://www.ncbi.nlm.nih.gov/gene/367 (Accessed on 15.09.2022).
[46]
Tan MHE, Li J, Xu HE, Melcher K, Yong E. Androgen receptor: Structure, role in prostate cancer and drug discovery. Acta Pharmacol Sin 2015; 36(1): 3-23.
[http://dx.doi.org/10.1038/aps.2014.18] [PMID: 24909511]
[47]
Yoo S, Pettersson A, Jordahl KM, et al. Androgen receptor CAG repeat polymorphism and risk of TMPRSS2:ERG-positive prostate cancer. Cancer Epidemiol Biomarkers Prev 2014; 23(10): 2027-31.
[http://dx.doi.org/10.1158/1055-9965.EPI-14-0020] [PMID: 24925673]
[48]
Available from: https://www.news-medical.net/health/What-is-TMPRSS2.aspx (Accessed on 01.10.2022.)
[49]
Wambier CG, Goren A. SARS-COV-2 infection is likely to be androgen mediated. J Am Acad Dermatol 2020; 83: 308-9.
[http://dx.doi.org/10.1016/j.jaad.2020.04.032] [PMID: 32283245]
[50]
Dutta S, Sengupta P. SARS-CoV-2 and male infertility: Possible multifaceted pathology. Reprod Sci 2021; 28(1): 23-6.
[http://dx.doi.org/10.1007/s43032-020-00261-z] [PMID: 32651900]
[51]
Ni W, Yang X, Yang D, et al. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Crit Care 2020; 24(1): 422.
[http://dx.doi.org/10.1186/s13054-020-03120-0] [PMID: 32660650]
[52]
Fan C, Lu W, Li K, Ding Y, Wang J. ACE2 expression in kidney and testis may cause kidney and testis infection in COVID-19 patients. Front Med 2021; 7: 563893.
[http://dx.doi.org/10.3389/fmed.2020.563893] [PMID: 33521006]
[53]
Available from: https://www.ncbi.nlm.nih.gov/gene/59272 (Accessed on 5.10.2022).
[54]
Available from: https://www.ncbi.nlm.nih.gov/gene/50943 (Accessed on 5.10.2022).
[55]
Available from: https://www.ncbi.nlm.nih.gov/gene/51284 (Accessed on 5.10.2022).
[56]
Davies DA, Adlimoghaddam A, Albensi BC. The Effect of COVID-19 on NF-κB and Neurological Manifestations of Disease. Mol Neurobiol 2021; 58(8): 4178-87.
[http://dx.doi.org/10.1007/s12035-021-02438-2] [PMID: 34075562]
[57]
Available from: https://www.ncbi.nlm.nih.gov/gene/79576 (Accessed on 5.10.2022).
[58]
Available from: https://www.ncbi.nlm.nih.gov/gene/51311 (Accessed on 5.10.2022).
[59]
Khanmohammadi S, Rezaei N. Role of Toll‐like receptors in the pathogenesis of COVID‐19. J Med Virol 2021; 93(5): 2735-9.
[http://dx.doi.org/10.1002/jmv.26826] [PMID: 33506952]
[60]
Singh AK, Singh A, Shaikh A, Singh R, Misra A. Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries. Diabetes Metab Syndr 2020; 14(3): 241-6.
[http://dx.doi.org/10.1016/j.dsx.2020.03.011] [PMID: 32247211]
[61]
Singh TU, Parida S, Lingaraju MC, Kesavan M, Kumar D, Singh RK. Drug repurposing approach to fight COVID-19. Pharmacol Rep 2020; 72(6): 1479-508.
[http://dx.doi.org/10.1007/s43440-020-00155-6] [PMID: 32889701]
[62]
Zou P, Wang X, Yang W, et al. Mechanisms of stress-induced spermatogenesis impairment in male rats following unpredictable chronic mild stress (uCMS). Int J Mol Sci 2019; 20(18): 4470.
[http://dx.doi.org/10.3390/ijms20184470] [PMID: 31510090]
[63]
El-sayed M. Changes in reproductive organs, semen characteristics and intra-testicular oxidative stress in adult male rats caused by azithromycin. Inter J Pharma Toxi 2017; 5: 72-9.
[64]
Al-Qadhi. Effect of Azithromycin on Sperm DNA of Male Rats Biol Med (Aligarh) 2022.
[65]
Wallach EE, Schlegel PN, Chang TSK, Marshall FF. Antibiotics: potential hazards to male fertility. Fertil Steril 1991; 55(2): 235-42.
[http://dx.doi.org/10.1016/S0015-0282(16)54108-9] [PMID: 1991524]
[66]
El-Sayed M, Kandiel M, Ebied D. Changes in reproductive organs, semen characteristics and intra-testicular oxidative stress in adult male rats caused by azithromycin. Int J Pharmacol Toxicol 2017; 5(2): 72-9.
[http://dx.doi.org/10.14419/ijpt.v5i2.7778]
[67]
Mark GPMG. ‘Disorders of male reproduction and male hypogonadism’ in John Firth. In: Christopher Conlon, and Timothy Cox. Oxford Textbook of Medicine 2020.
[68]
Marques P, Skorupskaite K, Rozario KS, et al. Physiology of GnRH and gonadotropin secretion. In: Feingold KR, Anawalt B Eds. Endotext [Internet] South Dartmouth. MDTextcom. 2000.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy