Hydrocephalus and arthrogryposis in an immunocompetent mouse model of ZIKA teratogeny: a developmental study

dc.creatorXavier-Neto, Jose
dc.creatorCarvalho, Murilo
dc.creatorPascoalino, Bruno Dos Santos
dc.creatorCardoso, Alisson Campos
dc.creatorCosta, Ângela Maria Sousa
dc.creatorPereira, Ana Helena Macedo
dc.creatorSantos, Luana Nunes
dc.creatorSaito, Ângela
dc.creatorMarques, Rafael Elias
dc.creatorSmetana, Juliana Helena Costa
dc.creatorConsonni, Silvio Roberto
dc.creatorBandeira, Carla
dc.creatorCosta, Vivian Vasconcelos
dc.creatorBajgelman, Marcio Chaim
dc.creatorOliveira, Paulo Sérgio Lopes de
dc.creatorCordeiro, Marli Tenorio
dc.creatorGonzales Gil, Laura Helena Vega
dc.creatorPauletti, Bianca Alves
dc.creatorGranato, Daniela Campos
dc.creatorPaes Leme, Adriana Franco
dc.creatorFreitas-Junior, Lucio
dc.creatorHolanda de Freitas, Carolina Borsoi Moraes
dc.creatorTeixeira, Mauro Martins
dc.creatorBevilacqua, Estela
dc.creatorFranchini, Kleber
dc.date2017-06-26T14:23:58Z
dc.date2017-06-26T14:23:58Z
dc.date2017
dc.date.accessioned2023-09-27T00:15:33Z
dc.date.available2023-09-27T00:15:33Z
dc.identifierXAVIER-NETO, J. et al. Hydrocephalus and arthrogryposis in an immunocompetent mouse model of ZIKA teratogeny: A developmental study. PLoS neglected tropical diseases, v. 11, n. 2, p. e0005363, fev. 2017.
dc.identifier1935-2735
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/19508
dc.identifier10.1371/journal.pntd.0005363
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8899042
dc.descriptionThe teratogenic mechanisms triggered by ZIKV are still obscure due to the lack of a suitable animal model. Here we present a mouse model of developmental disruption induced by ZIKV hematogenic infection. The model utilizes immunocompetent animals from wild-type FVB/NJ and C57BL/6J strains, providing a better analogy to the human condition than approaches involving immunodeficient, genetically modified animals, or direct ZIKV injection into the brain. When injected via the jugular vein into the blood of pregnant females harboring conceptuses from early gastrulation to organogenesis stages, akin to the human second and fifth week of pregnancy, ZIKV infects maternal tissues, placentas and embryos/fetuses. Early exposure to ZIKV at developmental day 5 (second week in humans) produced complex manifestations of anterior and posterior dysraphia and hydrocephalus, as well as severe malformations and delayed development in 10.5 days post-coitum (dpc) embryos. Exposure to the virus at 7.5-9.5 dpc induces intra-amniotic hemorrhage, widespread edema, and vascular rarefaction, often prominent in the cephalic region. At these stages, most affected embryos/fetuses displayed gross malformations and/or intrauterine growth restriction (IUGR), rather than isolated microcephaly. Disrupted conceptuses failed to achieve normal developmental landmarks and died in utero. Importantly, this is the only model so far to display dysraphia and hydrocephalus, the harbinger of microcephaly in humans, as well as arthrogryposis, a set of abnormal joint postures observed in the human setting. Late exposure to ZIKV at 12.5 dpc failed to produce noticeable malformations. We have thus characterized a developmental window of opportunity for ZIKV-induced teratogenesis encompassing early gastrulation, neurulation and early organogenesis stages. This should not, however, be interpreted as evidence for any safe developmental windows for ZIKV exposure. Late developmental abnormalities correlated with damage to the placenta, particularly to the labyrinthine layer, suggesting that circulatory changes are integral to the altered phenotypes.
dc.formatapplication/pdf
dc.languagepor
dc.rightsopen access
dc.subjectZika virus
dc.subjectModelos animais
dc.subjectArtrogripose
dc.subjectZika virus
dc.subjectModels, Animal
dc.subjectArthrogryposis
dc.subjectZika virus
dc.subjectModelos Animais
dc.subjectArtrogripose
dc.titleHydrocephalus and arthrogryposis in an immunocompetent mouse model of ZIKA teratogeny: a developmental study
dc.typeArticle


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