Single-cell transcriptome analysis of the novel coronavirus (SARS-CoV-2) associated gene ACE2 expression in normal and non-obstructive azoospermia (NOA) human male testes

Abstract

Being infected by SARS-CoV-2 may cause damage to multiple organs in patients, such as the lung, liver and heart. Angiotensin-converting enzyme 2 (ACE2), reported as a SARS-CoV-2 receptor, is also expressed in human male testes. This suggests a potential risk in human male reproductive system. However, the characteristics of ACE2-positive cells and the expression of other SARS-CoV-2 process-related genes are still worthy of further investigation. Here, we performed singlecell RNA seq (scRNA-seq) analysis on 853 male embryo primordial germ cells (PGCs) and 2,854 normal testis cells to assess the effects of the SARS-CoV-2 virus on the male reproductive system from embryonic stage to adulthood. We also collected and constructed the scRNA-seq library on 228 Sertoli cells from three non-obstructive azoospermia (NOA) patients to assess the effects at disease state. We found that ACE2 expressing cells existed in almost all testis cell types and Sertoli cells had highest expression level and positive cells ratio. Moreover, ACE2 was also expressed in human male PGCs. In adulthood, the level of ACE2 expression decreased with the increase of age. We also found that ACE2 positive cells had high expressions of stress response and immune activation-related genes. Interestingly, some potential SARS-CoV-2 process-related genes such as TMPRSS2, BSG, CTSL and CTSB had different expression patterns in the same cell type. Furthermore, ACE2 expression level in NOA donors' Sertoli cells was significantly decreased. Our work would help to assess the risk of SARS-CoV-2 infection in the male reproductive system. . Single-cell transcriptome analysis of the novel coronavirus (SARS-CoV-2) associated gene ACE2 expression in normal and non-obstructive azoospermia (NOA) human male testes. Sci China Life Sci 63, https://doi.

Alimentary System is Directly Attacked by SARS-COV-2 and Further Prevents Immune Dysregulation Caused by COVID-19

“…It's worth noting that the lung is a "frothy" organ and ACE2 is merely expressed on AT2 cells, protein and mRNA expressions of ACE2 might seem quite trivial compared to those expressed in solid organs. Our study also found trial mRNA and bare protein of AT2 in the lung, similar to other studies (10,11). We did, however, assume that the bioinformatic analysis was more applicable to other solid organs.…”

“…Serum ferritin, ALT, AST, ALP, GGT was the highest in digestive system symptom group. Studies have proved that the major functional binding receptor ACE2 has rather limited expressions in hepatocytes and cholangiocytes (11), which was against liver as a primary SARS-COV-2 target. That gastrointestinal injury itself can cause an increase in liver enzymes could not be ruled out in this situation (23).…”

ACE2 interaction networks in COVID-19: a physiological framework for prediction of outcome in patients with cardiovascular risk factors

“…Moreover, we found in the genitourinary tract the highest expression of TMPRSS2 gene that is known to positively regulate viral entry into the host cell via proteolytic cleavage of ACE2. In fact, there are studies supporting the high expression of ACE2 in the urogenital tissues [49][50][51] and endocrine tissues [52], additionally, there are increasing evidence of symptoms, like male infertility [53][54], urinary tract inflammation linked to viral cystitis [55], and transmission of the virus through urine [56]. On the other hand, so far qPCR experiments to detect SARS-CoV-2 in semen and testicular biopsy didn’t find signs of virus infection [50].…”

Alimentary System is Directly Attacked by SARS-COV-2 and Further Prevent Immune Dysregulation Caused by COVID-19

“…Serum ferritin, ALT, AST, ALP, GGT was the highest in digestive system symptom group. Studies have proved that the major functional binding receptor ACE2 has rather limited expressions in hepatocytes and cholangiocytes (11), which was against liver as a primary SARS-COV-2 target. That gastrointestinal injury itself can cause an increase in liver enzymes could not be ruled out in this situation (23).…”