COVID-19 disrupts the blood–testis barrier through the induction of inflammatory cytokines and disruption of junctional proteins

• Published in: Inflammation research Vol. 70; no. 10-12; pp. 1165 - 1175
• Main Authors: Peirouvi, Tahmineh, Aliaghaei, Abbas, Eslami Farsani, Bahram, Ziaeipour, Sanaz, Ebrahimi, Vahid, Forozesh, Mehdi, Ghadipasha, Masoud, Mahmoudiasl, Gholam-Reza, Aryan, Arefeh, Moghimi, Negin, Abdi, Shabnam, Raoofi, Amir, Kargar Godaneh, Mohammadhossein, Abdollahifar, Mohammad-Amin
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2021; Springer Nature B.V
• Subjects: Allergology; Autopsies; Autopsy; Biomedical and Life Sciences; Biomedicine; Blood; Blood-Testis Barrier - pathology; Claudins - metabolism; Complications; Connexin 43; Connexin 43 - metabolism; Coronaviruses; COVID-19; COVID-19 - pathology; Cytokines; Cytokines - metabolism; Dermatology; Fertility; Humans; Immunocytochemistry; Immunohistochemistry; Immunology; Infections; Inflammation; Interleukin 1; Interleukin 6; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Lung - pathology; Lungs; Male; Middle Aged; Neurology; Occludin - metabolism; Original Research Paper; Pharmacology/Toxicology; Protein expression; Proteins; Respiratory diseases; Rheumatology; RNA, Viral - analysis; Sertoli cells; Sertoli Cells - pathology; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spermatogenesis; Stereology; Testes; Testis - pathology; Tissues; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Viral diseases; COVID-19; Blood–testis barrier; Inflammatory cytokines
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-021-01497-4

Objective Junctional proteins are the most important component of the blood-testis barrier and maintaining the integrity of this barrier is essential for spermatogenesis and male fertility. The present study elucidated the effect of SARS-CoV-2 infection on the blood–testis barrier (BTB) in patients who died from severe acute respiratory syndrome coronavirus 2 (COVID-19) complications. Methods In this study, lung and testis tissue was collected from autopsies of COVID-19 positive ( n  = 10) and negative men ( n  = 10) and was taken for stereology, immunocytochemistry, and RNA extraction. Results Evaluation of the lung tissue showed that the SARS-CoV-2 infection caused extensive damage to the lung tissue and also increases inflammation in testicular tissue and destruction of the testicular blood barrier. Autopsied testicular specimens of COVID-19 showed that COVID-19 infection significantly changes the spatial arrangement of testicular cells and notably decreased the number of Sertoli cells. Moreover, the immunohistochemistry results showed a significant reduction in the protein expression of occluding, claudin-11, and connexin-43 in the COVID-19 group. In addition, we also observed a remarkable enhancement in protein expression of CD68 in the testes of the COVID-19 group in comparison with the control group. Furthermore, the result showed that the expression of TNF-α, IL1β, and IL6 was significantly increased in COVID-19 cases as well as the expression of occludin, claudin-11, and connexin-43 was decreased in COVID-19 cases. Conclusions Overall, the present study demonstrated that SARS-CoV-2 could induce the up-regulation of the pro-inflammatory cytokine and down-regulation of junctional proteins of the BTB, which can disrupt BTB and ultimately impair spermatogenesis.