High SARS-CoV-2 tropism and activation of immune cells in the testes of non-vaccinated deceased COVID-19 patients

Página do item simplificado
dc.contributor.authorCosta, Guilherme M. J.
dc.contributor.authorLacerda, Samyra M. S. N.
dc.contributor.authorFigueiredo, André F. A.
dc.contributor.authorWnuk, Natália T.
dc.contributor.authorBrener, Marcos R. G.
dc.contributor.authorAndrade, Lídia M.
dc.contributor.authorCampolina-Silva, Gabriel H.
dc.contributor.authorKauffmann-Zeh, Andrea
dc.contributor.authorPacifico, Lucila G. G.
dc.contributor.authorVersiani, Alice F.
dc.contributor.authorAntunes, Maísa M.
dc.contributor.authorSouza, Fernanda R.
dc.contributor.authorCassali, Geovanni D.
dc.contributor.authorCaldeira-Brant, André L.
dc.contributor.authorChiarini-Garcia, Hélio
dc.contributor.authorde Souza, Fernanda G.
dc.contributor.authorCosta, Vivian V.
dc.contributor.authorda Fonseca, Flavio G.
dc.contributor.authorNogueira, Maurício L.
dc.contributor.authorCampos, Guilherme R. F.
dc.contributor.authorKangussu, Lucas M.
dc.contributor.authorMartins, Estefânia M. N.
dc.contributor.authorAntonio, Loudiana M.
dc.contributor.authorBittar, Cintia [UNESP]
dc.contributor.authorRahal, Paula [UNESP]
dc.contributor.authorAguiar, Renato S.
dc.contributor.authorMendes, Bárbara P.
dc.contributor.authorProcópio, Marcela S.
dc.contributor.authorFurtado, Thiago P.
dc.contributor.authorGuimaraes, Yuri L.
dc.contributor.authorMenezes, Gustavo B.
dc.contributor.authorMartinez-Marchal, Ana
dc.contributor.authorOrwig, Kyle E.
dc.contributor.authorBrieño-Enríquez, Miguel
dc.contributor.authorFurtado, Marcelo H.
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.contributor.institutionClínica MF Fertilidade Masculina
dc.contributor.institutionFaculdade de Medicina de São Jose do Rio Preto
dc.contributor.institutionUniversity of Texas Medical Branch
dc.contributor.institutionUniversity of Pittsburgh School of Medicine
dc.contributor.institutionCentro de Desenvolvimento da Tecnologia Nuclear-CDTN/CNEN
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.date.accessioned2023-07-29T16:05:49Z
dc.date.available2023-07-29T16:05:49Z
dc.date.issued2023-12-01
dc.description.abstractBackground: Cellular entry of SARS-CoV-2 has been shown to rely on angiotensin-converting enzyme 2 (ACE2) receptors, whose expression in the testis is among the highest in the body. Additionally, the risk of mortality seems higher among male COVID-19 patients, and though much has been published since the first cases of COVID-19, there remain unanswered questions regarding SARS-CoV-2 impact on testes and potential consequences for reproductive health. We investigated testicular alterations in non-vaccinated deceased COVID-19-patients, the precise location of the virus, its replicative activity, and the immune, vascular, and molecular fluctuations involved in the pathogenesis. Results: We found that SARS-CoV-2 testicular tropism is higher than previously thought and that reliable viral detection in the testis requires sensitive nanosensors or RT-qPCR using a specific methodology. Through an in vitro experiment exposing VERO cells to testicular macerates, we observed viral content in all samples, and the subgenomic RNA’s presence reinforced the replicative activity of SARS-CoV-2 in testes of the severe COVID-19 patients. The cellular structures and viral particles, observed by transmission electron microscopy, indicated that macrophages and spermatogonial cells are the main SARS-CoV-2 lodging sites, where new virions form inside the endoplasmic reticulum Golgi intermediate complex. Moreover, we showed infiltrative infected monocytes migrating into the testicular parenchyma. SARS-CoV-2 maintains its replicative and infective abilities long after the patient’s infection. Further, we demonstrated high levels of angiotensin II and activated immune cells in the testes of deceased patients. The infected testes show thickening of the tunica propria, germ cell apoptosis, Sertoli cell barrier loss, evident hemorrhage, angiogenesis, Leydig cell inhibition, inflammation, and fibrosis. Conclusions: Our findings indicate that high angiotensin II levels and activation of mast cells and macrophages may be critical for testicular pathogenesis. Importantly, our findings suggest that patients who become critically ill may exhibit severe alterations and harbor the active virus in the testes.en
dc.description.affiliationUniversidade Federal de Minas Gerais, MG
dc.description.affiliationClínica MF Fertilidade Masculina, MG
dc.description.affiliationFaculdade de Medicina de São Jose do Rio Preto, SP
dc.description.affiliationDepartment of Pathology University of Texas Medical Branch
dc.description.affiliationDepartment of Obstetrics Gynecology and Reproductive Sciences Magee-Women’s Research Institute University of Pittsburgh School of Medicine
dc.description.affiliationCentro de Desenvolvimento da Tecnologia Nuclear-CDTN/CNEN, MG
dc.description.affiliationUniversidade Estadual Paulista, SP
dc.description.affiliationDepartamentos de Urologia e de Reprodução Humana da Rede Mater Dei de Saúde, MG
dc.description.affiliationUnespUniversidade Estadual Paulista, SP
dc.description.sponsorshipPró-Reitoria de Pesquisa, Universidade Federal de Minas Gerais
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
dc.description.sponsorshipFerring Pharmaceuticals
dc.description.sponsorshipIdFAPESP: # 2019/07250-9
dc.description.sponsorshipIdFAPESP: #2020/04836- 0
dc.description.sponsorshipIdCNPq: 312688/2017-2
dc.description.sponsorshipIdCNPq: 439119/2018-9
dc.description.sponsorshipIdFAPEMIG: APQ-01078-21
dc.description.sponsorshipIdFAPEMIG: CBB- APQ-04295- 17
dc.description.sponsorshipIdFAPEMIG: CBB-APQ-03081-17
dc.description.sponsorshipIdFerring Pharmaceuticals: Ferring COVID-19 Investigational Grant
dc.description.sponsorshipIdFAPEMIG: RED-00079-22
dc.description.sponsorshipIdFAPEMIG: RED-00135-22
dc.description.sponsorshipIdFAPEMIG: TEC - RED-00282-16
dc.identifierhttp://dx.doi.org/10.1186/s12915-022-01497-8
dc.identifier.citationBMC Biology, v. 21, n. 1, 2023.
dc.identifier.doi10.1186/s12915-022-01497-8
dc.identifier.issn1741-7007
dc.identifier.scopus2-s2.0-85148252494
dc.identifier.urihttp://hdl.handle.net/11449/249663
dc.language.isoeng
dc.relation.ispartofBMC Biology
dc.sourceScopus
dc.subjectInfertility
dc.subjectLeydig cell
dc.subjectMacrophages
dc.subjectNanotechnology
dc.subjectRenin-angiotensin system
dc.subjectSARS-CoV-2 replication
dc.subjectSertoli cell
dc.subjectSpermatogenesis
dc.subjectSpermatogonia
dc.subjectTestosterone
dc.titleHigh SARS-CoV-2 tropism and activation of immune cells in the testes of non-vaccinated deceased COVID-19 patientsen
dc.typeArtigo
unesp.author.orcid0000-0002-2907-7760[1]
unesp.author.orcid0000-0003-4577-6243[2]
unesp.author.orcid0000-0002-5650-6743[13]
unesp.author.orcid0000-0002-7523-7868[15]
unesp.author.orcid0000-0002-0175-642X[17]
unesp.author.orcid0000-0003-1102-2419[19]
unesp.author.orcid0000-0003-3678-118X[21]
unesp.author.orcid0000-0001-5180-3717[26]
unesp.author.orcid0000-0001-9887-3616[31]
unesp.author.orcid0000-0002-7952-8419[33]
unesp.author.orcid0000-0002-8806-0918[34]
unesp.author.orcid0000-0001-7499-4202[35]

Arquivos

Coleções

Artigos - Biologia - IBILCE