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Direct and Indirect Effects of SARS-CoV-2 on Human Testicular Cells

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Title:Direct and Indirect Effects of SARS-CoV-2 on Human Testicular Cells
Authors:Regaspi, Nicolas
Contributors:Verma, Saguna (advisor)
Nerurkar, Vivek (instructor)
Sy, Angela (instructor)
Keywords:SARS-CoV-2 virus
Human Testicular Cells
Date Issued:13 Aug 2021
Abstract:Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense single-stranded RNA virus; binding to cells robust in angiotensin-converting enzyme 2 (ACE2), a membrane-bound receptor widely expressed in testes. Studies indicate that SARS-CoV-2 infection disproportionately affects men with 2-3 times more death and severe disease irrespective of co-morbid conditions. Testes-associated pathogenesis in COVID-19 patients includes scrotal discomfort, interstitial edema, thinning of seminiferous tubules, reduced testosterone production, and impaired spermatogenesis. Despite clinical manifestations, the underlying mechanisms of testicular injury are currently unknown.
Objective: This study aims to characterize direct and indirect effects of SARS-CoV-2 infection in Leydig (LC), Sertoli (SC), and Seminiferous tubule (STC) cells.
Methods: For direct exposure, SC, LC, and STC were infected* with SARS-CoV-2 (MOI 1), and virus replication kinetics were measured via plaque assay and RT-PCR. For indirect exposure, STCs were exposed to (A) supernatant from SARS-CoV-2 infected human airway epithelial cells (HAE) and (B) SARS-CoV-2 spike (S) and envelope (E) proteins. Cells were exposed at 6hrs (A), 4hrs (B), and 24hrs(A and B), then tested for cell viability. RNA was extracted for measuring cytokine expression via RT-PCR at all time points. *(S. Giannakopoulos conducted direct virus infection experiments.)
Results: Direct infection of SC, LC, and STC with SARS-CoV-2 did not result in active virus replication despite high levels of ACE2. Plaque assay of STC and LC indicated no infectious virions. For indirect exposure of STC with infected SARS-CoV-2 HAE supernatant containing cytokines (TNFA, IL6, IFIT, INF1B), the results illustrate reduced viability by 26% (p<0.01) and TNFA induction. Exposure of STC with E protein (1 ug/mL and 4 ug/mL) induced cytotoxicity and significantly reduced cell viability at both concentrations (p<0.0001). E protein exposure promotes robust expression of inflammatory markers, IL-1B and IL-6.
Conclusions: The data suggest ACE2 expression in primary testicular cells does not support productive SARS-CoV-2 replication or direct induction of pro-inflammatory mediators. Systemic inflammation may indicate an indirect effect on testicular cells. SARS-CoV-2 E protein induces significant STC death and greatly up-regulates cytokine expression.
Rights:Attribution-NoDerivs 3.0 United States
Appears in Collections: MHRT Poster Session 2021

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