Fig. 7

Hypothetical viral and molecular mechanisms of testis infection and damage by SARS-CoV-2. a SARS-CoV-2 (green color) was identified in spermatogonial cells (Spg), Sertoli cells (SC), Leydig cells (LC), infiltrative monocytes (Mono), macrophages (MΦ), spermatocytes (sptc), and spermatids (sptd). Note viral factories in macrophages and spermatogonial cells (green arrows). A direct influence of SARS-CoV-2 in testicular cells hampers ACE2 activity, while activation of mast cells (chymase positive) elevates the levels of angiotensin II (a potent pro-inflammatory molecule) (asterisks). Angiogenic and inflammatory factors can induce the infiltration and activation of mast cells. High levels of angiotensin II, activation of mast cells, and inflammatory factors can activate (polarize) macrophages. The testicular phenotype of COVID-19 patients (fibrosis, vascular alteration, inflammation, tunica propria thickening, Sertoli cell barrier loss, germ cell apoptosis, and inhibition of Leydig cells) can be linked to elevated angiotensin II and active mast cells and macrophages. b Genes network related to angiotensin II, activated mast cells, and macrophages (pink box) extracted from STRING (https://string-db.org/). These three elements upregulate the inflammatory, apoptotic, fibrotic, and vascular genes while downregulating critical seminiferous tubule and Leydig cell genes. Red arrows: upregulated genes; green arrows: downregulated genes; ~: genes upregulated and downregulated depending on the phase