{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T08:05:00Z","timestamp":1759133100440,"version":"3.37.3"},"reference-count":52,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Juvenile Diabetes Research Foundation & nPOD-V"},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","award":["PE-2013-02357094"],"award-info":[{"award-number":["PE-2013-02357094"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Context<\/jats:title><jats:p>Infection by SARS-CoV-2 may be associated with testicular dysfunction that could affect male fertility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>Testicles of fatal COVID-19 cases were investigated to detect virus in tissue and to evaluate histopathological and transcriptomic changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1210\/clinem\/dgac608","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T17:08:27Z","timestamp":1666199307000},"page":"950-961","source":"Crossref","is-referenced-by-count":11,"title":["Autopsy Study of Testicles in COVID-19: Upregulation of Immune-Related Genes and Downregulation of Testis-Specific Genes"],"prefix":"10.1210","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6888-7080","authenticated-orcid":false,"given":"Alessio","family":"Basolo","sequence":"first","affiliation":[{"name":"Obesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa , 56124 Pisa , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anello Marcello","family":"Poma","sequence":"additional","affiliation":[{"name":"Department of Surgical, 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