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

Ma, Ling; Xie, Wen; Li, Danyang; Shi, Lei; Mao, Yanhong; Xiong, Yao; Zhang, Yuanzhen; Zhang, Ming

doi:10.1101/2020.03.21.20037267

Cited by 267 publications

(293 citation statements)

References 21 publications

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“…Additionally, stromal cells in reproductive system (ovary and testis) and thyroid gland were also identified as potential target cells under the condition of viremia, suggesting potential injuries in these tissues. Actually, a recent study reported a significant change in certain male sex hormones in COVID-19 male patients [46], which is consistent with the notion that testis is potentially targeted by SARS-CoV-2.…”

Section: Discussionsupporting

confidence: 80%

Systemic analysis of tissue cells potentially vulnerable to SARS-CoV-2 infection by the protein-proofed single-cell RNA profiling of ACE2, TMPRSS2 and Furin proteases

Zhou

Niu²,

Jiang

et al. 2020

Preprint

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Single-cell RNA profiling of ACE2, the SARS-CoV-2 receptor, had proposed multiple tissue cells as the potential targets of SARS-CoV-2, the novel coronavirus causing the COVID-19 pandemic. However, most were not echoed by the patients' clinical manifestations, largely due to the lack of protein expression information of ACE2 and co-factors. Here, we incorporated the protein information to analyse the expression of ACE2, together with TMPRSS2 and Furin, two proteases assisting SARS-CoV-2 infection, at single cell level in situ, which we called protein-proofed single-cell RNA (pscRNA) profiling. Systemic analysis across 36 tissues revealed a rank list of candidate cells potentially vulnerable to SARS-CoV-2. The top targets are lung AT2 cells and macrophages, then cardiomyocytes and adrenal gland stromal cells, followed by stromal cells in testis, ovary and thyroid. Whereas, the polarized kidney proximal tubule cells, liver cholangiocytes and intestinal enterocytes are less likely to be the primary SARS-CoV-2 targets as ACE2 localizes at the apical region of cells, where the viruses may not readily reach. These findings are in concert with the clinical characteristics of prominent lung symptoms, frequent heart injury, and uncommon intestinal symptoms and acute kidney injury. Together, we provide a comprehensive view on the potential SARS-CoV-2 targets by pscRNA profiling, and propose that, in addition to acute respiratory distress syndrome, attentions should also be paid to the potential injuries in cardiovascular, endocrine and reproductive systems during the treatment of COVID-19 patients.

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Section: Discussionsupporting

confidence: 80%

Systemic analysis of tissue cells potentially vulnerable to SARS-CoV-2 infection by the protein-proofed single-cell RNA profiling of ACE2, TMPRSS2 and Furin proteases

Zhou

Niu²,

Jiang

et al. 2020

Preprint

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“…SARS is known to cause orchitis and destruction to male germ cells 38 . Similar effect from COVID-19 was speculated, but a most recent study had just provided the first direct evidence that SARS-CoV-2 infection impacts male sex hormones 39 . Similarly, small intestine is the tissue with the second highest level of ACE2 expression, while SARS-CoV-2 was found in stool samples of COVID-19 patients both in China and the United States 7,42 , even after the viral RNA decreased to undetectable level in respiratory tract 43 .…”

Section: Discussionmentioning

confidence: 57%

Atlas of ACE2 gene expression in mammals reveals novel insights in transmisson of SARS-Cov-2

Sun

et al. 2020

Preprint

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Background: COVID-19 has become a worldwide pandemic. It is caused by a novel coronavirus named SARS-CoV-2 with elusive origin. SARS-CoV-2 infects mammalian cells by binding to ACE2, a transmembrane protein. Therefore, the conservation of ACE2 and its expression pattern across mammalian species, which are yet to be comprehensively investigated, may provide valuable insights into tracing potential hosts of SARS-CoV-2. Methods:We analyzed gene conservation of ACE2 across mammals and collected more than 140 transcriptome datasets from human and common mammalian species, including presumed hosts of SARS-CoV-2 and other animals in close contact with humans. In order to enable comparisons across species and tissues, we used a unified pipeline to quantify and normalize ACE2 expression levels. Results:We first found high conservation of ACE2 genes among common mammals at both DNA and peptide levels, suggesting that a broad range of mammalian species can potentially be the hosts of SARS-CoV-2. Next, we showed that high level of ACE2 expression in certain human tissues is consistent with clinical symptoms of COVID-19 patients. Furthermore, we observed that ACE2 expressed in a species-specific manner in the mammals examined. Notably, high expression in skin and eyes in cat and dog suggested that these animals may play roles in transmitting SARS-CoV-2 to humans. Conclusions:Through building the first atlas of ACE2 expression in pets and livestock, we identified species and tissues susceptible to SARS-CoV-2 infection, yielding novel insights into the viral transmission.

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“…As one of the drug candidates against the epidemic, GS-5734 mainly exerts antiviral therapeutic effects against the COVID-19 virus. It has been reported that the COVID-19 virus has damaging effects on the male reproductive system and kidneys, such as orchitis and causing sterility (15,16). The balance between the treatment of reproductive damage caused by viruses and the reproductive toxicity caused by the drug may be an interesting research content.…”

Section: Discussionmentioning

confidence: 99%

A preliminary study on the reproductive toxicity of GS-5734 on male mice

Fan

Luo

Zhao

et al. 2020

Preprint

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Background: GS-5734 as a novel and promising medicine for COVID-2019, its biological impact on the mammalian reproductive system has not been systematically studied. The aim of this study was to evaluate the effects of GS-5734 on sperm parameters and spermatogenesis in mice. Materials and Methods:In this study, GS-5734 was synthesized according to the report. 28 adult male mice were randomly segregated into four groups (n=7 for each group). The group 1 was set as the control group, the group 1, 2, 3 and 4 were administered with GS-5734 at a daily dose of 0, 10, 50, 150 μ g/mouse respectively, by intraperitoneal injection for 10 days. On the 7th day after the last injection, the testes and cauda epididymides were collected for HE staining and sperm concentration, motility, morphology analysis. Results:The results indicated that after treated with GS-5734, the total sperm count and motile sperm rate showed downward trends, the abnormal sperm rate showed an increasing trend. As compared with the control group, GS-5734 at a daily dose of 150 μ g/mouse caused a significant decrease in sperm concentration and motility, and a significant increased of abnormal sperm rate; the 50 μ g/mouse drug treatment lead to a significant decrease in sperm motility and an increase in abnormal sperm rate. The HE staining of testicular and epididymal tissues showed that the spermatogenesis of mice was significantly deteriorated with the increasing dosage of GS-5734, especially in the 150 μ g/mouse group. Conclusion:Our findings suggest that a high dosage of GS-5734 may induce testicular toxicity and result in deterioration of sperm parameters in mice. More investigation on the reproductive toxicity of GS-5734 is required.

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

Cited by 267 publications

References 21 publications

Systemic analysis of tissue cells potentially vulnerable to SARS-CoV-2 infection by the protein-proofed single-cell RNA profiling of ACE2, TMPRSS2 and Furin proteases

Systemic analysis of tissue cells potentially vulnerable to SARS-CoV-2 infection by the protein-proofed single-cell RNA profiling of ACE2, TMPRSS2 and Furin proteases

Atlas of ACE2 gene expression in mammals reveals novel insights in transmisson of SARS-Cov-2

A preliminary study on the reproductive toxicity of GS-5734 on male mice

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