ACE2 receptor expression in testes: implications in coronavirus disease 2019 pathogenesis†

Abstract

Expression of angiotensin-converting enzyme 2, receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is high in the testes, therefore SARS-CoV-2 infection and its association with male reproductive health should be investigated in male coronavirus disease 2019 patients.

Keywords: ACE2; Leydig cells; SARS-CoV-2; cytokines and infertility; testis.

Figure 1

(A) Comparison of ACE2 and cells-specific gene expression in normal adult human testes (n = 3) using microarray profiling assay. It shows the average (standard error of mean) of intensity values of target genes, including ACE2 (Angiotensin I converting enzyme 2), Zbtb16 (Zinc finger and BTB domain containing 16; Plzf), Calb2 (calbindin 2; Calretinin), Sox9 (SRY-box transcription factor 9), Cd34, and house-keeping Polr2a (RNA polymerase II subunit A). (B) Hypothetical model of SARS-CoV-2 testicular infection based on data from other coronaviruses. ACE2 expressing LC in the interstitium are one of the targets of cell free SARS-CoV-2 infection that leads to LC dysfunction including impaired steroidogenesis, inflammatory response and/or apoptosis. SARS-CoV-2 also infects ACE expressing cells of seminiferous tubules including Sertoli cells (SC) and spermatogonia cells (Spg) that may cause production of inflammatory cytokines, transient blood–testis barrier disruption, and germ cell depletion thus leading to impaired spermatogenesis. SARS-CoV-2 infection-associated inflammatory response in the testes may result in increased recruitment of the peripheral immune cells including peripheral macrophages (PM) and virus-specific T cells (not shown here) that may facilitate virus clearance. Virus may not directly infect testicular macrophages (TM) but they play a role in suppressing the inflammatory response and limiting the testicular damage.