Autopsy Study of Testicles in COVID-19: Upregulation of Immune-Related Genes and Downregulation of Testis-Specific Genes

• Published in: The journal of clinical endocrinology and metabolism Vol. 108; no. 4; pp. 950 - 961
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.04.2023
• Subjects: Androgens; Autopsy; B cells; Biological response modifiers; Cell size; Comparative analysis; COVID-19; COVID-19 - metabolism; Down-Regulation; Fertility; Follicle-stimulating hormone; Genes; Genetic aspects; Genetic transcription; Genomes; Genomics; Health aspects; Heart; Humans; Hybridization; Immunohistochemistry; Infections; Interferon; Leukocytes; Luteinizing hormone; Lymphocytes T; Macrophages; Male; Nucleocapsids; RNA; RNA, Messenger - metabolism; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Spermatogenesis; T cells; Testes; Testis - pathology; Transcriptomics; Up-Regulation; Viral infections; Viruses; α-Interferon; COVID-19; SARS-CoV-2; testis-specific genes; testis; innate immunity; autopsy
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgac608

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.