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Abstract
In recent decades, a concerning worldwide decline in male fertility has been observed. While the exact cause remains unclear, this decline is most likely attributable to environmental exposures. Viruses and alcohol have both played a large role throughout human history and on male reproductive health. The COVID-19 pandemic has resulted in hundreds of millions of men infected with SARS-CoV-2. Additionally, alcohol use increased during the pandemic. These two exposures were chosen because of their immediate relevance. Two models were developed to explore how environmental exposures impact male reproductive health. The first is a blood-testis barrier model. It is made from primary Sertoli cells cultured on transwells creating a cell-formed barrier with culture medium on the top and bottom sides. The second is an advanced stem cell-based spermatogenesis model. It mimics the spatiotemporal aspects of the testis.
Using the blood-testis barrier model our research demonstrates that SARS-CoV-2 variants of concern can differentially impact the blood-testis barrier in multiple species. Furthermore, we show that clinically relevant levels of alcohol can reversibly disrupt the blood-testis barrier. Additionally, we propose diverse experimental frameworks to assess the impact of alcohol and SARS-CoV-2 infection in the blood-testis barrier and spermatogenesis models. These findings offer crucial insights and pave the way for future investigations into male reproductive health.