scRNA-seq Profiling of Human Testes Reveals the Presence of ACE2 Receptor, a Target for SARS-CoV-2 Infection, in Spermatogonia, Leydig and Sertoli Cells

Abstract

In December 2019, a novel coronavirus (SARS-CoV-2) was identified in patients with pneumonia (called COVID-19) in Wuhan, Hubei Province, China. SARS-CoV-2 shares high sequence similarity and uses the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), as does severe acute respiratory syndrome coronavirus (SARS-CoV). Several studies have provided bioinformatic evidence of potential routes for SARS-CoV-2 infection in respiratory, cardiovascular, digestive and urinary systems. However, whether the reproductive system is a potential target of SARS-CoV-2 infection has not been determined. Here, we investigate the expression pattern of ACE2 in adult human testis at the level of single-cell transcriptomes. The results indicate that ACE2 is predominantly enriched in spermatogonia, Leydig and Sertoli cells. Gene ontology analyses indicate that GO categories associated with viral reproduction and transmission are highly enriched in ACE2-positive spermatogonia while male gamete generation related terms are down-regulated. Cell-cell junction and immunity related GO terms are increased in ACE2-positive Leydig and Sertoli cells, but mitochondria and reproduction related GO terms are decreased. These findings provide evidence that human testes are a potential target of SARS-CoV-2 infection which may have significant impact on our understanding of the pathophysiology of this rapidly spreading disease.

Effect of SARS-CoV-2 infection upon male gonadal function: A single center-based study

“…Based on scRNA-seq analysis, Wang ZP et al found that TMPRSS2 mainly exists in spermatogonia and spermatids, whereas ACE2 widely expresses in spermatogonia, Leydig and Sertoli cells. Gene ontology (GO) enrichment analysis further indicated that GO categories associated with viral reproduction and transmission were positively enriched in ACE2-positive spermatogonia [9] . SARS, the similar virus of SARS-CoV-2, has been reported to cause orchitis [13] .…”

EZH2-mediated H3K27me3 inhibits ACE2 expression

“…ACE2 is enriched in the epithelia of lung [7], while single-cell RNA-seq data analysis of ACE2 expression reveals potential risks of more human organs vulnerable to SARS-CoV-2 infection [8]. In reproductive system, single-cell transcriptomes of adult human testis showed high expression of ACE2 in spermatogonia, Leydig and Sertoli cells [9]. Coronaviruses are prone to mutation and recombination due to their error-prone RNA-dependent RNA polymerase (RdRP) [10], and virus variation may allow some subtypes of the virus to better bind to the receptor ACE2.…”

Does COVID-19 affect male fertility?

“…Therefore, cells that show high level of ACE2 expression have the potential to be targeted and damaged by the virus [2]. Multiple studies detected high ACE2 expression level in testicular cells, mainly in seminiferous duct cells, spermatogonia, Leydig cell and Sertoli cells [2][3][4]. Based on the results of these studies, it is concluded that the testis could be a potential target for direct damage by SARS-COV2 virus.…”