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Updated: Nov 5, 2025

Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
Bioinformatic and mouse model reveal the potential high vulnerability of Leydig cells on SARS-CoV-2
Jiawei Zhang1, Yuqi Wu1, Shulin Li1
1Department of Urology and Carson International Cancer Center, Shenzhen University General Hospital and Shenzhen University Clinical Medical Academy Center, Shenzhen University, Shenzhen, China.
Background:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in China and spread rapidly since the end of 2019. Previous studies have confirmed that SARS-CoV-2 infects host cells via binding to angiotensin converting enzyme II (ACE2).
Methods:
To explore the expression of ACE2 and the potential risk of infection in testis, we performed a bioinformatic analysis based on public databases, and conducted a pilot study using a mouse model. We also collected clinical follow-up date on male patients who had recovered from COVID-19 for 6 months.
Results:
The results showed that the RNA expression of ACE2 was higher in testis compared with other organs. Single-cell analysis and immunocytochemistry further indicated that Leydig cells were at risk of SARS-CoV-2 infection. Green fluorescence was only detected in the Leydig cells after intratesticular injection of pseudovirus SARS-CoV-2 in the mouse model. In the clinical follow-up, serum total testosterone level was statistically lower in patients who had recovered from COVID-19 compared with healthy men (P=0.010).
Conclusions:
The findings of the present study indicate the potential vulnerability of Leydig cells. It is important to monitor the reproductive system and its complications in male COVID-19 patients. Further studies are still needed on SARS-CoV-2-associated reproductive complications.
Insights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may infect male reproductive cells, specifically Leydig cells, due to higher angiotensin converting enzyme II (ACE2) expression in the testes. This could impact testosterone levels in recovered COVID-19 patients.
Area of Science:
- Reproductive biology
- Virology
- Endocrinology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a global health concern.
- The virus utilizes angiotensin converting enzyme II (ACE2) to enter host cells.
- Understanding viral tropism and potential organ-specific risks is crucial.
Purpose of the Study:
- To investigate the expression of ACE2 in the testis.
- To assess the potential risk of SARS-CoV-2 infection in testicular Leydig cells.
- To evaluate the impact of COVID-19 on male reproductive health.
Main Methods:
- Bioinformatic analysis of public databases for ACE2 expression.
- Pilot study using a mouse model with intratesticular pseudovirus SARS-CoV-2 injection.
- Clinical follow-up of male COVID-19 recovered patients for 6 months.
Main Results:
- Testicular ACE2 RNA expression was significantly higher compared to other organs.
- Leydig cells showed vulnerability to SARS-CoV-2 infection, confirmed by single-cell analysis and immunocytochemistry.
- Male patients recovered from COVID-19 exhibited statistically lower serum total testosterone levels.
Conclusions:
- Leydig cells are a potential target for SARS-CoV-2, indicating vulnerability in the male reproductive system.
- Monitoring of the reproductive system and associated complications in male COVID-19 patients is recommended.
- Further research is necessary to elucidate SARS-CoV-2-associated reproductive complications.

