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.

In December 2019, a novel coronavirus (SARS-CoV-2) was identified in COVID-19 patients in Wuhan, Hubei Province, China. SARS-CoV-2 shares both high sequence similarity and the use of the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), with severe acute respiratory syndrome coronavirus (SARS-CoV). Several studies have provided bioinformatic evidence of potential routes of 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 yet been determined. Here, we investigate the expression pattern of ACE2 in adult human testes at the level of single-cell transcriptomes. The results indicate that ACE2 is predominantly enriched in spermatogonia and Leydig and Sertoli cells. Gene Set Enrichment Analysis (GSEA) indicates that Gene Ontology (GO) categories associated with viral reproduction and transmission are highly enriched in ACE2-positive spermatogonia, while male gamete generation related terms are downregulated. 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 the human testis is a potential target of SARS-CoV-2 infection, which may have significant impact on our understanding of the pathophysiology of this rapidly spreading disease.

BACKGROUND Analysis of prostate carcinoma cells isolated from the peripheral blood suggested a classification based on three categories. METHODS Centrifugation density gradients and magnetic cell sorting were used to isolate circulating prostate carcinoma cells from peripheral blood. Immunocytochemistry staining and fluorescent in situ hybridization allowed characterization of isolated cancer cells. RESULTS Terminal cells can be divided into 3 classes: 1) large, buoyant, fragile cells with a large nucleus that were captured in a 1.068 g/mL gradient; 2) enucleate cells (4,6‐diamidino‐2‐phenylindole [DAPI] negative) that were positive for cytokeratin and PSMA antibodies; and 3) cellular debris exhibiting cytokeratin and PSMA positive staining as well as nuclear debris identified by DAPI staining, which included cytoplasmic debris. Growing cells also exhibited three morphologic characteristics: those possessing stem cell–like morphology and characteristics such as small size, high density, developed cytokeratin systems, PSMA expression, and aneuploidy; those in M phase; and cell clusters. The majority of isolated cells exhibited intermediate characteristics and thus comprised the third group of circulating cancer cells. CONCLUSIONS Although the significance of the cluster remains undetermined, observation suggests that the cluster has the ability to circulate as a microtumor and subsequently arrest in the small veins and capillaries. It is hypothesized that the clusters could escape certain facets of immune surveillance and possibly gain a selective growth advantage over single cells in a distant site. Further hypothesis proposes that arrested cells recruit growth‐promoting nutrients, which would result in the invasion of local blood vessels and vascularization. Cancer 2000;88:2787–95. © 2000 American Cancer Society.

Background: Why only a few follicles are activated to enter the growing follicle pool each wave remains unclear. Results: TGF-␤ regulates oocyte growth through p70 S6 kinase 1/ribosomal protein S6 signaling. Conclusion: TGF-␤ participates in maintenance of the primordial follicle pool. Significance: Learning how TGF-␤ acts on primordial follicle growth.