SARS-CoV-2 Enters Human Leydig Cells and Affects Testosterone Production In Vitro

Li, Lü; Sottas, Chantal M.; Chen, Hsu-Yu; Li, Yuchang; Cui, Haoyi; Villano, Jason; Mankowski, Joseph L.; Cannon, Paula M.; Papadopoulos, Vassilios

doi:10.3390/cells12081198

Cited by 4 publications

(2 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The high expression level of ACE2 in various testicular cells, including vas deferens cells, spermatogonial cells, stromal cells, and sertoli cells, renders the testes highly susceptible to SARS-CoV-2 infection ( Fu et al., 2020 ; Hikmet et al., 2020 ; Wang and Xu, 2020 ; Qi et al., 2021 ; Ribeiro et al., 2023 ). Several in vitro and in vivo studies demonstrated the susceptibility of testicular cells to SARS-CoV-2 ( Campos et al., 2021 ; Mahé et al., 2023 ; Chen et al., 2023a ; Li et al., 2023b ). Due to the physiological barriers, SARS-CoV-2 could potentially persist in the semen of recovered patients ( Li et al., 2020a ).…”

Section: Long-term Effects Of Covid-19mentioning

confidence: 99%

Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects

Zhang,

Chen,

Tian

et al. 2024

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

SARS-CoV-2 is the causative virus of the devastating COVID-19 pandemic that results in an unparalleled global health and economic crisis. Despite unprecedented scientific efforts and therapeutic interventions, the fight against COVID-19 continues as the rapid emergence of different SARS-CoV-2 variants of concern and the increasing challenge of long COVID-19, raising a vast demand to understand the pathomechanisms of COVID-19 and its long-term sequelae and develop therapeutic strategies beyond the virus per se. Notably, in addition to the virus itself, the replication cycle of SARS-CoV-2 and clinical severity of COVID-19 is also governed by host factors. In this review, we therefore comprehensively overview the replication cycle and pathogenesis of SARS-CoV-2 from the perspective of host factors and host-virus interactions. We sequentially outline the pathological implications of molecular interactions between host factors and SARS-CoV-2 in multi-organ and multi-system long COVID-19, and summarize current therapeutic strategies and agents targeting host factors for treating these diseases. This knowledge would be key for the identification of new pathophysiological aspects and mechanisms, and the development of actionable therapeutic targets and strategies for tackling COVID-19 and its sequelae.

show abstract

Section: Long-term Effects Of Covid-19mentioning

confidence: 99%

Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects

Zhang,

Chen,

Tian

et al. 2024

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…In the cohorts of men who fell ill with COVID‐19 during the very first wave where dramatically reduced circulating tT levels had been found 16 and subsequently followed over time, the tT values progressively recovered, although the increase was very slow and eventually not even complete 17,18 . From a pathobiological standpoint it has been demonstrated that SARS‐Cov‐2 can damage Leydig cells, both structurally and functionally, thus justifying a real drop in circulating tT levels 13,19–24 . Thereof, it is possible to speculate that the viral replication could lead to tT decrease, which may result as a marker of unfavorable outcomes.…”

Section: Introductionmentioning

confidence: 99%

Is SARS‐CoV‐2‐induced disease a decisive factor influencing testosterone in males? Findings from a case‐control ex post facto study

Capogrosso,

Bertini,

Pontillo

et al. 2023

Andrology

View full text Add to dashboard Cite

BackgroundWhether the observed lower total testosterone (tT) levels in male patients with COVID‐19 are caused by a direct impact of SARS‐CoV‐2 infection or are collateral phenomena shared by other systemic inflammatory conditions has not yet been clarified.ObjectivesTo investigate the independent role of COVID‐19 in reducing circulating tT levels in men.Materials and methodsWe compared demographic, clinical, and hormonal values of patients with laboratory confirmed COVID‐19 admitted during the first wave of the pandemic with a cohort of consecutive male patients admitted to the intensive care unit (ICU) of the same academic center because of severe acute respiratory distress syndrome (ARDS) but without SARS‐CoV‐2 infection and no previous history of COVID‐19. Linear regression model tested the independent impact of COVID‐19 on circulating tT levels. Logistic regression model was used to test predictors of death in the entire cohort.ResultsOf 286 patients with COVID‐19, 70 men had been admitted to the ICU ( = cases) and were compared to 79 patients equally admitted to ICU because of severe ARDS but negative for SARS‐CoV‐2 infection and without previous history of COVID‐19 ( = controls). Controls were further grouped into noninfective (n = 49) and infective‐ARDS (n = 30) patients. At baseline, controls were older (p = 0.01) and had more comorbidities (p < 0.0001). Overall, cases admitted to ICU had significantly lower circulating tT levels compared to controls (0.9 nmol/L vs. 2.1 nmol/L; vs. 1.2 nmol/L; p = 0.03). At linear regression, being negative for COVID‐19 was associated with higher tT levels (Coeff: 2.13; 95% confidence interval ‐ CI 0.71‐3.56; p = 0.004) after adjusting for age, BMI, comorbidities and IL‐6 levels. Only age and IL‐6 levels emerged to be associated with higher risk of death regardless of COVID‐19 status.ConclusionsThis case‐control ex post facto study showed lower tT levels in men with COVID‐19 compared to those without COVID‐19 despite both groups have been equally admitted to ICU for severe ARDS, thus suggesting a possible direct impact of SARS‐CoV‐2 infection toward circulating tT levels and a consequent more severe clinical outcome.

show abstract

SARS-CoV-2 replicates in the human testis with slow kinetics and has no major deleterious effects ex vivo

Mahé,

Bourgeau,

da Silva

et al. 2023

J Virol

View full text Add to dashboard Cite

SARS-CoV-2, the etiological agent of the ongoing Covid-19 pandemic, is a respiratory virus that infects several organs beyond the lungs. The alterations of semen parameters, testicular morphology, and testosteronemia reported in Covid-19 patients, along with the high expression of SARS-CoV-2 main receptor ACE2 in the testis, raise questions about the underlying mechanisms. Using a previously validated ex vivo model of human testis, we show that SARS-CoV-2 infects ACE2-positive Leydig and Sertoli cells. Slow virus replication kinetics were observed, with a peak of infection at day 6 post-infection and a decline of infectious virions at day 9. The infection had no major impact on testicular morphology or main hormonal functions, but some steroidogenic enzymes were decreased at day 9. While antiviral effectors were upregulated, there was no transcriptional induction of key pro-inflammatory cytokines. Altogether, these data indicate that SARS-CoV-2 replication in the human testis ex vivo is limited and suggest that testicular damages in infected individuals are unlikely to result from direct deleterious effects of SARS-CoV-2 on this organ. IMPORTANCE SARS-CoV-2 is a new virus responsible for the Covid-19 pandemic. Although SARS-CoV-2 primarily affects the lungs, other organs are infected. Alterations of testosteronemia and spermatozoa motility in infected men have raised questions about testicular infection, along with high level in the testis of ACE2, the main receptor used by SARS-CoV-2 to enter host cells. Using an organotypic culture of human testis, we found that SARS-CoV-2 replicated with slow kinetics in the testis. The virus first targeted testosterone-producing Leydig cells and then germ-cell nursing Sertoli cells. After a peak followed by the upregulation of antiviral effectors, viral replication in the testis decreased and did not induce any major damage to the tissue. Altogether, our data show that SARS-CoV-2 replicates in the human testis to a limited extent and suggest that testicular damages in infected patients are more likely to result from systemic infection and inflammation than from viral replication in the testis.

show abstract

SARS-CoV-2 Enters Human Leydig Cells and Affects Testosterone Production In Vitro

Cited by 4 publications

References 62 publications

Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects

Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects

Is SARS‐CoV‐2‐induced disease a decisive factor influencing testosterone in males? Findings from a case‐control ex post facto study

SARS-CoV-2 replicates in the human testis with slow kinetics and has no major deleterious effects ex vivo

Contact Info

Product

Resources

About