P-002 SARS-CoV-2 tropism spectrum for human testicular cells

Abstract Study question In human testicular cells, how are SARS-CoV-2 receptors and their priming proteases for the viral spike (S) protein distributed spatially? Summary answer Human tissue expressed both severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) investigated, key factors cellular susceptibility to entry/infection. What is known already Male reproductive function altered on numerous levels by coronavirus disease. Angiotensin-converting enzyme 2 (ACE2) main host membrane receptor but requires transmembrane protease serine (TMPRSS2) S (activation proteolysis). Other proteases, like cathepsin L (CTSL), might nevertheless contribute entrance. This mostly happens in cells with low or nonexistent ACE2 expression, which calls alternative cluster of differentiation 147 (CD147). Although co-expression essential successful infection, it still unknown accompanying geographically cells. design, size, duration To overcome this restriction, we focused using immunohistochemistry map spatial distribution CD147, as well protein, TMPRSS2 CTSL, necessary fusion tissue. Participants/materials, setting, methods Laboratory experiments were executed under Joint Ethics Committee Hospital University (approval number 2020-094 (077-DEFI-078-CE)). tissues obtained from cases presenting Sertoli cell syndrome, maturation arrest, hypospermatogenesis at Pathology department, five patients per pathology. Formalin-fixed paraffin-embedded sections 4 μm incubated anti-antibodies (orb638860, 1:100 1:150, Byorbit), (ab109131, 1:1000, Abcam), CD147 (MA5-29060, 1:2500, Invitrogen) CTSL (MA5-32602, 1:100, Invitrogen). Main results role chance The present study did not intend virus entry proteins different pathologies. As spermatogenesis a complex process involving many intricately linked selected these syndromes specifically identify individual more clearly, cell-only cases, spermatocytes arrest spermatids cases. group consisted whose azoospermia was due duct obstruction, showing conserved spermatogenesis. Interstitial including endothelium, Leydig myoid peritubular seminiferous epithelium (Sertoli spermatogonia, spermatocytes, spermatids), discovered contain TMPRSS2, demonstrating all All types, exception endothelium showed presence whereas only found Leydig, peritubular, result, co-expressed CTSL. findings proteomic databases indicating have supported our discoveries, that may be directly infected injured, halting acting vectors SARS-CoV-2. Limitations, reasons caution Our support tropism raise possibility manifestations, although does necessarily mean infects further studies needed discern infection transmission targeting underlying mechanisms. Wider implications system infections has long been demonstrated. prevent allowing attach germ impair sperm production, increase risk meiotic errors viruses spreading through sperm, emphasizes importance safe practices wider community. Trial registration applicable