{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:05:28Z","timestamp":1792785928172,"version":"4.5.0"},"reference-count":67,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"European Union\u2019s Horizon 2020","award":["733176"],"award-info":[{"award-number":["733176"]}]},{"name":"European Union\u2019s Horizon 2020","award":["734584"],"award-info":[{"award-number":["734584"]}]},{"name":"ZIKAlliance","award":["734548"],"award-info":[{"award-number":["734548"]}]},{"name":"Inserm and the University of Rennes","id":[{"id":"https:\/\/ror.org\/015m7wh34","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n STUDY QUESTION<\/jats:title>\n Can human epididymis and efferent ducts (ED) support Zika virus (ZIKV) replication ex vivo and act as a source of prolonged viral shedding in semen of infected men?<\/jats:p>\n <\/jats:sec>\n \n SUMMARY ANSWER<\/jats:title>\n Our novel ex vivo models demonstrate that ZIKV exhibits segment-specific tropism, with sustained replication in the ED epithelium and restricted infection of epididymal stromal macrophages, identifying these organs as distinct reservoirs for viral persistence in semen.<\/jats:p>\n <\/jats:sec>\n \n WHAT IS KNOWN ALREADY<\/jats:title>\n The 2015\u20132017 ZIKV outbreak revealed that the virus persists in semen and can be sexually transmitted by men long after the acute phase of infection. While the human testis is an established reservoir, animal studies and longitudinal semen analyses suggest that additional organs within the male genital tract contribute to the prolonged excretion of infectious ZIKV. However, the specific roles of the human EDs and epididymis have remained unexplored due to the lack of physiologically relevant human models.<\/jats:p>\n <\/jats:sec>\n \n STUDY DESIGN, SIZE, DURATION<\/jats:title>\n Organotypic cultures of human EDs and epididymis corpus (EC) were developed and characterized using post-mortem tissues obtained from 11 uninfected organ donors (age range 29\u201379\u2009years, median age: 58\u2009years). Using this innovative ex vivo platform, we investigated ZIKV replication kinetics, cellular tropism, and the resulting impact on tissue viability and innate immune responses over a 9-day culture period.<\/jats:p>\n <\/jats:sec>\n \n PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n ED and EC tissues were dissected and cultured on PET inserts at the air\/medium interface. Tissue integrity was validated via histology, lactate dehydrogenase (LDH) viability assays, and transcriptomic\/protein marker expression, assessed by RT-qPCR and immunohistochemistry. Explants were exposed to ZIKV, with replication monitored via viral RNA (vRNA) quantification, as assessed by RT-qPCR, and plaque assays for infectious virion release. Cellular targets were identified using RNAscope combined with immunohistochemistry. To determine the impact of the infection, we analyzed the innate immune response by RT-qPCR and ELISA and cell viability by LDH assays and cleaved caspase 3 expression, as well as the transcriptional and protein expression of a selected panel of cell markers, assessed by RT-qPCR and immunohistochemistry.<\/jats:p>\n <\/jats:sec>\n \n MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n The ex vivo models preserved global tissue architecture, viability, and the expression of epithelial, macrophage and smooth muscle markers throughout the study. ZIKV infected the ED epithelium, with replicative vRNA persisting from 3\u2009days post-infection (dpi) until the end of culture (P\u2009=\u20090.01). Conversely, in the EC, infection was limited to stromal macrophages and smooth muscle cells, peaking at 3\u2009dpi before diminishing (P\u2009=\u20090.002). Both segments exhibited robustly repeatable results across donors. Notably, both ED and EC exhibited limited antiviral responses and weak pro-inflammatory responses to ZIKV infection. ZIKV replication did not induce significant changes in morphology, viability or functional marker expression, suggesting a non-cytopathic infection mechanism.<\/jats:p>\n <\/jats:sec>\n \n LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n While these organotypic cultures preserved multi-lineage cell types for 9\u2009days, epithelial morphology and organization were gradually impacted, and the expression of a subset of functional and hormone-responsive markers (e.g. AQP1, ESR1, AR) decreased. Furthermore, the ex vivo setup cannot replicate in vivo viral entry via systemic circulation or luminal flow from the testis, nor can it account for the influence of infiltrating systemic leukocytes and global inflammation.<\/jats:p>\n <\/jats:sec>\n \n WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n These novel human ED and EC culture systems bridge a critical gap in reproductive research. Our findings reveal a dual cellular pathway for ZIKV shedding, epithelial in the ED and macrophage-mediated in the EC, offering a mechanistic explanation for the prolonged presence of ZIKV in human semen. Furthermore, this ex vivo platform provides a new tool for studying male reproductive tract-pathogen interactions, as well as the efficacy of antiviral drugs.<\/jats:p>\n <\/jats:sec>\n \n FUNDING<\/jats:title>\n This study received funding from the European Union\u2019s Horizon 2020 research and innovation program under grant agreement no. 733176, ZikaPLAN (grant agreement no. 734584) and ZIKAlliance (grant agreement no. 734548), and was funded in part by Inserm and the University of Rennes.<\/jats:p>\n <\/jats:sec>\n \n DISCLOSURES<\/jats:title>\n We declare no conflict of interest.<\/jats:p>\n <\/jats:sec>\n \n TRIAL REGISTRATION NUMBER<\/jats:title>\n N\/A.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/humrep\/deag141","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T11:42:01Z","timestamp":1787398921000},"source":"Crossref","is-referenced-by-count":0,"title":["Novel\n ex vivo<\/i>\n models reveal segment-specific infection of the human efferent ducts and epididymis: implications for Zika virus persistence and shedding in semen"],"prefix":"10.1093","author":[{"given":"J","family":"da Silva","sequence":"first","affiliation":[{"name":"Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en sant\u00e9, environnement et travail) - UMR_S 1085 , Rennes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A P","family":"Satie","sequence":"additional","affiliation":[{"name":"Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en sant\u00e9, environnement et travail) - UMR_S 1085 , Rennes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Houzet","sequence":"additional","affiliation":[{"name":"Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en sant\u00e9, environnement et travail) - UMR_S 1085 , Rennes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M J","family":"Lista Brotos","sequence":"additional","affiliation":[{"name":"Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en sant\u00e9, environnement et travail) - UMR_S 1085 , Rennes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Mathieu","sequence":"additional","affiliation":[{"name":"Service d\u2019Urologie, Centre Hospitalier Universitaire de Rennes , Rennes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Goepp","sequence":"additional","affiliation":[{"name":"Coordination hospitali\u00e8re des pr\u00e9l\u00e8vements d\u2019organes et de tissus, Centre Hospitalier de Vannes , Vannes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Aubry","sequence":"additional","affiliation":[{"name":"Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en sant\u00e9, environnement et travail) - UMR_S 1085 , Rennes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1788-2690","authenticated-orcid":false,"given":"N","family":"Dejucq-Rainsford","sequence":"additional","affiliation":[{"name":"Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en sant\u00e9, environnement et travail) - UMR_S 1085 , Rennes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"2026091808353202600_deag141-B1800","article-title":"ZIKA virus entry mechanisms in human cells","volume":"69","year":"2019","journal-title":"Infect Genet Evol"},{"key":"2026091808353202600_deag141-B1","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1093\/infdis\/jiab001","article-title":"Risk of sexually transmitted Zika virus in a cohort of economically disadvantaged urban residents","volume":"224","author":"Aguilar Ticona","year":"2021","journal-title":"J Infect Dis"},{"key":"2026091808353202600_deag141-B2","doi-asserted-by":"crossref","first-page":"e0010566","DOI":"10.1371\/journal.pntd.0010566","article-title":"Zika virus persistence in the male macaque reproductive tract","volume":"16","author":"Ball","year":"2022","journal-title":"PLoS Negl Trop Dis"},{"key":"2026091808353202600_deag141-B3","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1111\/andr.13509","article-title":"Immunoregulatory mechanisms between epithelial clear cells and mononuclear phagocytes in the epididymis","volume":"12","author":"Battistone","year":"2024","journal-title":"Andrology"},{"key":"2026091808353202600_deag141-B4","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/molehr\/gav066","article-title":"Expression profiles of human epididymis epithelial cells reveal the functional diversity of caput, corpus and cauda regions","volume":"22","author":"Browne","year":"2016","journal-title":"Mol Hum Reprod"},{"key":"2026091808353202600_deag141-B5","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S1473-3099(19)30678-4","article-title":"1 year after acute Zika virus infection in men","volume":"20","author":"Bujan","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"2026091808353202600_deag141-B6","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/andr.13706","article-title":"Mild coronavirus disease 2019: results of a multicentric prospective study on severe acute respiratory syndrome coronavirus 2 presence in semen fractions and cells and its effects on semen parameters","volume":"13","author":"Bujan","year":"2025","journal-title":"Andrology"},{"key":"2026091808353202600_deag141-B7","doi-asserted-by":"crossref","first-page":"21557","DOI":"10.1038\/s41598-023-48493-8","article-title":"Detection and persistence of Zika virus in body fluids and associated factors: a prospective cohort study","volume":"13","author":"Calvet","year":"2023","journal-title":"Sci Rep"},{"key":"2026091808353202600_deag141-B8","doi-asserted-by":"crossref","first-page":"e1006537","DOI":"10.1371\/journal.ppat.1006537","article-title":"Zika virus preferentially replicates in the female reproductive tract after vaginal inoculation of rhesus macaques","volume":"13","author":"Carroll","year":"2017","journal-title":"PLoS Pathog"},{"key":"2026091808353202600_deag141-B9","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1093\/humrep\/14.6.1522","article-title":"Androgen regulation of glycosidase secretion in epithelial cell cultures from human epididymis","volume":"14","author":"Castell\u00f3n","year":"1999","journal-title":"Hum Reprod"},{"key":"2026091808353202600_deag141-B10","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/labinvest.2016.116","article-title":"CD68\/macrosialin: not just a histochemical marker","volume":"97","author":"Chistiakov","year":"2017","journal-title":"Lab Invest"},{"key":"2026091808353202600_deag141-B11","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/humupd\/dmn055","article-title":"New insights into epididymal biology and function","volume":"15","author":"Cornwall","year":"2009","journal-title":"Hum Reprod Update"},{"key":"2026091808353202600_deag141-B12","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1016\/j.celrep.2017.01.056","article-title":"Frequent Zika virus sexual transmission and prolonged viral RNA shedding in an immunodeficient mouse model","volume":"18","author":"Duggal","year":"2017","journal-title":"Cell Rep"},{"key":"2026091808353202600_deag141-B13","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1089\/ten.tec.2013.0061","article-title":"Essential components for ex vivo proliferation of mesenchymal stromal cells","volume":"20","author":"Fekete","year":"2014","journal-title":"Tissue Eng Part C Methods"},{"key":"2026091808353202600_deag141-B14","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/nature20556","article-title":"Zika virus infection damages the testes in mice","volume":"540","author":"Govero","year":"2016","journal-title":"Nature"},{"key":"2026091808353202600_deag141-B15","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.3201\/eid2308.170036","article-title":"High infection rates for adult macaques after intravaginal or intrarectal inoculation with Zika virus","volume":"23","author":"Haddow","year":"2017","journal-title":"Emerg Infect Dis"},{"key":"2026091808353202600_deag141-B16","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/B978-0-12-801238-3.64593-2","volume-title":"Encyclopedia of Reproduction. Efferent Ductules: structure and Function","author":"Hess","year":"2018"},{"key":"2026091808353202600_deag141-B17","doi-asserted-by":"crossref","first-page":"5377","DOI":"10.3390\/ijms21155377","article-title":"The role of the epididymis and the contribution of epididymosomes to mammalian reproduction","volume":"21","author":"James","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2026091808353202600_deag141-B18","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1016\/S1473-3099(17)30444-9","article-title":"Effect of acute Zika virus infection on sperm and virus clearance in body fluids: a prospective observational study","volume":"17","author":"Joguet","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"2026091808353202600_deag141-B1900","article-title":"Probing Molecular Insights into Zika Virus\u2013Host Interactions","volume":"10","year":"2018","journal-title":"Viruses"},{"key":"2026091808353202600_deag141-B19","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/andr.12745","article-title":"Differential gene expression profiles of human efferent ducts and proximal epididymis","volume":"8","author":"L\u00e9gar\u00e9","year":"2020","journal-title":"Andrology"},{"key":"2026091808353202600_deag141-B20","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1210\/jcem-51-3-423","article-title":"Testosterone and some of its precursors and metabolites in the human epididymis","volume":"51","author":"Leinonen","year":"1980","journal-title":"J Clin Endocrinol Metab"},{"key":"2026091808353202600_deag141-B21","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.fertnstert.2014.11.022","article-title":"Characterization of primary cultures of adult human epididymis epithelial cells","volume":"103","author":"Leir","year":"2015","journal-title":"Fertil Steril"},{"key":"2026091808353202600_deag141-B22","doi-asserted-by":"crossref","first-page":"e202000744","DOI":"10.26508\/lsa.202000744","article-title":"An atlas of human proximal epididymis reveals cell-specific functions and distinct roles for CFTR","volume":"3","author":"Leir","year":"2020","journal-title":"Life Sci Alliance"},{"key":"2026091808353202600_deag141-B23","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s00441-020-03208-7","article-title":"An organoid model to assay the role of CFTR in the human epididymis epithelium","volume":"381","author":"Leir","year":"2020","journal-title":"Cell Tissue Res"},{"key":"2026091808353202600_deag141-B24","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1152\/physrev.00021.2019","article-title":"From Ancient to Emerging Infections: the Odyssey of Viruses in the Male Genital Tract","volume":"100","author":"Le Tortorec","year":"2020","journal-title":"Physiol Rev"},{"key":"2026091808353202600_deag141-B25","first-page":"63","article-title":"Insulin-transferrin-selenium as a novel serum-free media supplement for the culture of human amnion mesenchymal stem cells","volume":"49","author":"Liu","year":"2019","journal-title":"Ann Clin Lab Sci"},{"key":"2026091808353202600_deag141-B26","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/j.cell.2016.11.016","article-title":"Zika virus causes testis damage and leads to male infertility in mice","volume":"167","author":"Ma","year":"2016","journal-title":"Cell"},{"key":"2026091808353202600_deag141-B27","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.3201\/eid3012.231733","article-title":"Effect of sexual partnerships on Zika virus transmission in virus-endemic region, Northeast Brazil","volume":"30","author":"Magalhaes","year":"2024","journal-title":"Emerg Infect Dis"},{"key":"2026091808353202600_deag141-B28","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1093\/infdis\/jiaa563","article-title":"Follow-up household serosurvey in Northeast Brazil for Zika virus: sexual contacts of index patients have the highest risk for seropositivity","volume":"223","author":"Magalhaes","year":"2021","journal-title":"J Infect Dis"},{"key":"2026091808353202600_deag141-B29","doi-asserted-by":"crossref","first-page":"e0110423","DOI":"10.1128\/jvi.01104-23","article-title":"SARS-CoV-2 replicates in the human testis with slow kinetics and has no major deleterious effects ex vivo","volume":"97","author":"Mah\u00e9","year":"2023","journal-title":"J Virol"},{"key":"2026091808353202600_deag141-B30","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/S1473-3099(20)30834-3","article-title":"Long-term Zika virus infection of non-sperm cells in semen","volume":"20","author":"Mah\u00e9","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"2026091808353202600_deag141-B31","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S1473-3099(16)00138-9","article-title":"Zika virus: high infectious viral load in semen, a new sexually transmitted pathogen?","volume":"16","author":"Mansuy","year":"2016","journal-title":"Lancet Infect Dis"},{"key":"2026091808353202600_deag141-B32","doi-asserted-by":"crossref","first-page":"4697","DOI":"10.1172\/JCI121735","article-title":"Zika virus infects human testicular tissue and germ cells","volume":"128","author":"Matusali","year":"2018","journal-title":"J Clin Invest"},{"key":"2026091808353202600_deag141-B33","doi-asserted-by":"crossref","first-page":"e0006691","DOI":"10.1371\/journal.pntd.0006691","article-title":"Infection of epididymal epithelial cells and leukocytes drives seminal shedding of Zika virus in a mouse model. In Shi","volume":"12","author":"McDonald","year":"2018","journal-title":"PLoS Negl Trop Dis"},{"key":"2026091808353202600_deag141-B34","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1056\/NEJMoa1711038","article-title":"Zika virus shedding in semen of symptomatic infected men","volume":"378","author":"Mead","year":"2018","journal-title":"N Engl J Med"},{"key":"2026091808353202600_deag141-B35","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.celrep.2016.12.045","article-title":"Axl mediates ZIKA virus entry in human glial cells and modulates innate immune responses","volume":"18","author":"Meertens","year":"2017","journal-title":"Cell Rep"},{"key":"2026091808353202600_deag141-B36","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.3201\/eid2806.212317","article-title":"Effects of acute dengue infection on sperm and virus clearance in body fluids of men","volume":"28","author":"Mons","year":"2022","journal-title":"Emerg Infect Dis"},{"key":"2026091808353202600_deag141-B37","doi-asserted-by":"crossref","first-page":"1001.e1","DOI":"10.1016\/j.cmi.2017.07.006","article-title":"Detection of Zika virus RNA in semen of asymptomatic blood donors","volume":"23","author":"Musso","year":"2017","journal-title":"Clin Microbiol Infect"},{"key":"2026091808353202600_deag141-B38","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1042\/BC20040078","article-title":"Aquaporin-1 and -9 are differentially regulated by oestrogen in the efferent ductule epithelium and initial segment of the epididymis","volume":"97","author":"Oliveira","year":"2005","journal-title":"Biol Cell"},{"key":"2026091808353202600_deag141-B39","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1056\/NEJMc1607583","article-title":"Prolonged shedding of Zika virus associated with congenital infection","volume":"375","author":"Oliveira","year":"2016","journal-title":"N Engl J Med"},{"key":"2026091808353202600_deag141-B40","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1038\/nm.4206","article-title":"Zika viral dynamics and shedding in rhesus and cynomolgus macaques","volume":"22","author":"Osuna","year":"2016","journal-title":"Nat Med"},{"key":"2026091808353202600_deag141-B41","doi-asserted-by":"crossref","first-page":"e01434-19","DOI":"10.1128\/JVI.01434-19","article-title":"Zika virus infection, reproductive organ targeting, and semen transmission in the male olive baboon","volume":"94","author":"Peregrine","year":"2019","journal-title":"J Virol"},{"key":"2026091808353202600_deag141-B42","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.virol.2020.01.015","article-title":"Zika virus-spread, epidemiology, genome, transmission cycle, clinical manifestation, associated challenges, vaccine and antiviral drug development","volume":"543","author":"Pielnaa","year":"2020","journal-title":"Virology"},{"key":"2026091808353202600_deag141-B43","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1093\/biolre\/ioab113","article-title":"Self-renewal and differentiation of rat epididymal basal cells using a novel in vitro organoid model\u2020","volume":"105","author":"Pinel","year":"2021","journal-title":"Biol Reprod"},{"key":"2026091808353202600_deag141-B44","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1038\/s41467-021-22729-5","article-title":"Epididymal epithelium propels early sexual transmission of Zika virus in the absence of interferon signaling","volume":"12","author":"Pletnev","year":"2021","journal-title":"Nat Commun"},{"key":"2026091808353202600_deag141-B45","doi-asserted-by":"crossref","first-page":"e82193","DOI":"10.7554\/eLife.82193","article-title":"The regional distribution of resident immune cells shapes distinct immunological environments along the murine epididymis","volume":"11","author":"Pleuger","year":"2022","journal-title":"eLife"},{"key":"2026091808353202600_deag141-B46","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1093\/humrep\/del018","article-title":"Human testis in organotypic culture: application for basic or clinical research","volume":"21","author":"Roulet","year":"2006","journal-title":"Hum Reprod"},{"key":"2026091808353202600_deag141-B47","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/S0015-0282(16)37502-1","article-title":"Duration of transit of spermatozoa through the human male ductular system","volume":"21","author":"Rowley","year":"1970","journal-title":"Fertil Steril"},{"key":"2026091808353202600_deag141-B48","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1093\/biolre\/ioaa137","article-title":"Zika virus in rhesus macaque semen and reproductive tract tissues: a pilot study of acute infection\u2020","volume":"103","author":"Schmidt","year":"2020","journal-title":"Biol Reprod"},{"key":"2026091808353202600_deag141-B49","doi-asserted-by":"crossref","first-page":"e0009211","DOI":"10.1371\/journal.pntd.0009211","article-title":"Zika virus disrupts the barrier structure and absorption\/secretion functions of the epididymis in mice","volume":"15","author":"Sheng","year":"2021","journal-title":"PLoS Negl Trop Dis"},{"key":"2026091808353202600_deag141-B50","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3109\/01485018108999321","article-title":"Testosterone, dihydrotestosterone, and zinc concentrations in human testis and epididymis","volume":"7","author":"Suescun","year":"1981","journal-title":"Arch Androl"},{"key":"2026091808353202600_deag141-B51","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1111\/andr.12633","article-title":"Revisiting structure\/functions of the human epididymis","volume":"7","author":"Sullivan","year":"2019","journal-title":"Andrology"},{"key":"2026091808353202600_deag141-B52","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1093\/humupd\/dmw015","article-title":"The human epididymis: its function in sperm maturation","volume":"22","author":"Sullivan","year":"2016","journal-title":"Hum Reprod Update"},{"key":"2026091808353202600_deag141-B53","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/S0022-5347(17)53912-9","article-title":"Proliferation of human prostatic epithelial cells in culture: aspects of identification","volume":"127","author":"Syms","year":"1982","journal-title":"J Urol"},{"key":"2026091808353202600_deag141-B54","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.1016\/j.celrep.2016.11.070","article-title":"A mouse model of Zika virus sexual transmission and vaginal viral replication","volume":"17","author":"Tang","year":"2016","journal-title":"Cell Rep"},{"key":"2026091808353202600_deag141-B55","doi-asserted-by":"crossref","first-page":"e1008601","DOI":"10.1371\/journal.ppat.1008601","article-title":"Zika virus tropism during early infection of the testicular interstitium and its role in viral pathogenesis in the testes","volume":"16","author":"Tsetsarkin","year":"2020","journal-title":"PLoS Pathog"},{"key":"2026091808353202600_deag141-B56","doi-asserted-by":"crossref","first-page":"5350","DOI":"10.1038\/s41467-018-07782-x","article-title":"Routes of Zika virus dissemination in the testis and epididymis of immunodeficient mice","volume":"9","author":"Tsetsarkin","year":"2018","journal-title":"Nat Commun"},{"key":"2026091808353202600_deag141-B57","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1111\/andr.13732","article-title":"Human efferent ductules and epididymis display unique cell lineages with motile and primary cilia","volume":"13","author":"Vinay","year":"2025","journal-title":"Andrology"},{"key":"2026091808353202600_deag141-B58","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.virol.2021.05.001","article-title":"Persistence of Zika virus RNA in the epididymis of the murine male reproductive tract","volume":"560","author":"Vogt","year":"2021","journal-title":"Virology"},{"key":"2026091808353202600_deag141-B59","doi-asserted-by":"crossref","first-page":"531","DOI":"10.4103\/aja.aja_11_19","article-title":"The epididymal immune balance: a key to preserving male fertility","volume":"21","author":"Voisin","year":"2019","journal-title":"Asian J Androl"},{"key":"2026091808353202600_deag141-B60","first-page":"4:309","article-title":"Recent advances in the study of the structure and function of the epididymis","author":"Wang","year":"2024","journal-title":"Explor Immunol"},{"key":"2026091808353202600_deag141-B61","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12929-023-00906-6","article-title":"CLEC5A mediates Zika virus-induced testicular damage","volume":"30","author":"Wang","year":"2023","journal-title":"J Biomed Sci"},{"key":"2026091808353202600_deag141-B62","author":"WHO","year":"2024"},{"key":"2026091808353202600_deag141-B63","doi-asserted-by":"crossref","first-page":"2300466","DOI":"10.1080\/22221751.2023.2300466","article-title":"Immunocompetent mouse models revealed that S100A4+ monocytes\/macrophages facilitate long-term Zika virus infection in the testes","volume":"13","author":"Yang","year":"2024","journal-title":"Emerg Microbes Infect"},{"key":"2026091808353202600_deag141-B64","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/j.cell.2016.08.004","article-title":"Vaginal exposure to Zika virus during pregnancy leads to fetal brain infection","volume":"166","author":"Yockey","year":"2016","journal-title":"Cell"},{"key":"2026091808353202600_deag141-B65","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.3389\/fimmu.2020.02115","article-title":"The immune characteristics of the epididymis and the immune pathway of the epididymitis caused by different pathogens","volume":"11","author":"Zhao","year":"2020","journal-title":"Front Immunol"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/humrep\/advance-article-pdf\/doi\/10.1093\/humrep\/deag141\/71224873\/deag141.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/humrep\/advance-article-pdf\/doi\/10.1093\/humrep\/deag141\/71224873\/deag141.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:35:45Z","timestamp":1789734945000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/advance-article\/doi\/10.1093\/humrep\/deag141\/8817169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":67,"URL":"https:\/\/doi.org\/10.1093\/humrep\/deag141","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,18]]},"article-number":"deag141"}}