Dissertation Defense Seminar:”In-vivo and in-vitro investigation of SARS-CoV-2 associated injury and functional impairments in the testis”, Stefanos Giannakopoulos, PhD Candidate

When

12/01/2023    
12:30 PM - 1:30 PM

Where

JABSOM Medical Education Bldg., Rm 314
651 Ilalo St., Honolulu,, HI, 96813

Event Type

In Person & By Zoom

Zoom Link: https://hawaii.zoom.us/j/98685877294
Call in: (669) 900-6833
Zoom ID: 986 8587 7294
Passcode: 536167

Stefanos Giannakopoulos
Ph.D. Candidate
Department of Cell and Molecular Biology
John A. Burns School of Medicine
University of Hawaiʻi at Mānoa


Traditionally associated with shortness of breath and lung injury, the 2019 severe-acute respiratory syndrome coronavirus 2 pandemic presented several other alarming features in COVID-19 patients, including cytokine storm and injury of other organs such as the kidney and testis. Infected males also experienced symptoms such as orchitis, erectile dysfunction, reduced testosterone levels, and low sperm count. These testicular symptoms are accompanied by leukocyte infiltration, sloughing of the seminiferous tubules, and germ cell death. Cohorts of studies from COVID-19 moderate, severe, and critical patients have revealed additional hormone alterations as well as functional damages to function of the male reproductive tract. These include decreased semen volume, lower sperm count, decreased testosterone, follicular stimulating hormone, and luteinizing hormone. While most of these parameters recover rapidly upon recovery from the disease, long-term follow up of recovered patients suffering from long-COVID revealed lower testosterone levels and reduced sperm parameters up to 12 months after disease onset. Therefore, it is still unclear what the mechanism of testicular injury is and what are the specific immune mechanisms responsible for contributing to SARS-CoV-2 testicular short-term and long-term pathogenesis. We here demonstrate that human testis cannot support productive SARS-CoV-2 infection. This suggests that the mechanism of testicular injury observed in COVID-19 patients is a bystander effect of infection. We utilized different 2D and 3D testicular models, optimized in our lab, to characterize the effect of the SARS-CoV-2 infection-derived inflammatory mediators and antigens, on the testicular cells. We also use K18-hACE2 mice to characterize various aspects of testicular pathogenesis associated with SARS-CoV-2 in vivo. These include histopathology studies during the acute stage and short-term after recovery and the correlation between systemic cytokine storm and different markers of testicular injury and function. Lastly, we used high throughput RNA-seq approach to identify the molecular signatures associated with SARS-CoV-2 infection in the K18-hACE2 mouse testis. The outcome of this study provides significant mechanistic insights into the testicular injury and effects during the acute and recovery stage of SARS-CoV-2 on testicular function. It also addresses fundamental gaps in our understanding of how this virus affects male reproductive health.