Context Infection by SARS-CoV-2 may be associated with testicular dysfunction that could affect male fertility. Objective Testicles of fatal COVID-19 cases were investigated to detect virus in tissue and to evaluate histopathological and transcriptomic changes. Methods Three groups were compared: (a) uninfected controls (subjects dying of trauma or sudden cardiac death; n = 10); (b) subjects dying of COVID-19 (virus-negative in testes; n = 15); (c) subjects dying of COVID-19 (virus-positive in testes; n = 9). SARS-CoV-2 genome and nucleocapsid antigen were probed using RT-PCR, in situ hybridization, and immunohistochemistry (IHC). Infiltrating leukocytes were typed by IHC. mRNA transcripts of immune-related and testis-specific genes were quantified using the nCounter method. Results SARS-CoV-2 was detected in testis tissue of 9/24 (37%) COVID-19 cases accompanied by scattered T-cell and macrophage infiltrates. Size of testicles and counts of spermatogenic cells were not significantly different among groups. Analysis of mRNA transcripts showed that in virus-positive testes immune processes were activated (interferon-alpha and -gamma pathways). By contrast, transcription of 12 testis-specific genes was downregulated, independently of virus positivity in tissue. By IHC, expression of the luteinizing hormone/choriogonadotropin receptor was enhanced in virus-positive compared to virus-negative testicles, while expression of receptors for androgens and the follicle-stimulating hormone were not significantly different among groups. Conclusion In lethal COVID-19 cases, infection of testicular cells is not uncommon. Viral infection associates with activation of interferon pathways and downregulation of testis-specific genes involved in spermatogenesis. Due to the exceedingly high numbers of infected people in the pandemic, the impact of virus on fertility should be further investigated.

AUTOPSY STUDY OF TESTICLES IN COVID-19: UPREGULATION OF IMMUNE-RELATED GENES AND DOWNREGULATION OF TESTIS-SPECIFIC GENES

Basolo, Alessio;Poma, Anello Marcello;Macerola, Elisabetta;Salvetti, Alessandra;Vignali, Paola;Torregrossa, Liborio;Evangelisti, Laura;Sparavelli, Rebecca;Giannini, Riccardo;Ugolini, Clara;Basolo, Fulvio;Santini, Ferruccio;
2022-01-01

Abstract

Context Infection by SARS-CoV-2 may be associated with testicular dysfunction that could affect male fertility. Objective Testicles of fatal COVID-19 cases were investigated to detect virus in tissue and to evaluate histopathological and transcriptomic changes. Methods Three groups were compared: (a) uninfected controls (subjects dying of trauma or sudden cardiac death; n = 10); (b) subjects dying of COVID-19 (virus-negative in testes; n = 15); (c) subjects dying of COVID-19 (virus-positive in testes; n = 9). SARS-CoV-2 genome and nucleocapsid antigen were probed using RT-PCR, in situ hybridization, and immunohistochemistry (IHC). Infiltrating leukocytes were typed by IHC. mRNA transcripts of immune-related and testis-specific genes were quantified using the nCounter method. Results SARS-CoV-2 was detected in testis tissue of 9/24 (37%) COVID-19 cases accompanied by scattered T-cell and macrophage infiltrates. Size of testicles and counts of spermatogenic cells were not significantly different among groups. Analysis of mRNA transcripts showed that in virus-positive testes immune processes were activated (interferon-alpha and -gamma pathways). By contrast, transcription of 12 testis-specific genes was downregulated, independently of virus positivity in tissue. By IHC, expression of the luteinizing hormone/choriogonadotropin receptor was enhanced in virus-positive compared to virus-negative testicles, while expression of receptors for androgens and the follicle-stimulating hormone were not significantly different among groups. Conclusion In lethal COVID-19 cases, infection of testicular cells is not uncommon. Viral infection associates with activation of interferon pathways and downregulation of testis-specific genes involved in spermatogenesis. Due to the exceedingly high numbers of infected people in the pandemic, the impact of virus on fertility should be further investigated.
2022
Basolo, Alessio; Poma, Anello Marcello; Macerola, Elisabetta; Bonuccelli, Diana; Proietti, Agnese; Salvetti, Alessandra; Vignali, Paola; Torregrossa, Liborio; Evangelisti, Laura; Sparavelli, Rebecca; Giannini, Riccardo; Ugolini, Clara; Basolo, Fulvio; Santini, Ferruccio; Toniolo, Antonio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1159243
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