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The geographic distribution of CZS in Brazil during the 2015\u20132017 outbreak was asymmetrical, with a higher prevalence in the Northeast and Central\u2010West regions of the country, despite the ubiquitous distribution of the vector <jats:italic>Aedes aegypti,<\/jats:italic> indicating that environmental factors could influence ZIKV vertical transmission and\/or severity. Here we investigate the involvement of the most used agrochemicals in Brazil with CZS. First, we exposed human neuroblastoma SK\u2010N\u2010AS cells to the 15 frequently used agrochemical molecules or derivative metabolites able to cross the blood\u2013brain barrier. We found that a derived metabolite from a widely used herbicide in the Central\u2010West region, 2,4\u2010dichlorophenoxyacetic acid (2,4D), exacerbates ZIKV neurotoxic effects in vitro. We validate this observation by demonstrating vertical transmission leading to microcephaly in the offspring of immunocompetent C57BL\/6J mice exposed to water contaminated with 0.025\u2009mg\/L of 2,4D. Newborn mice whose dams were exposed to 2,4D and infected with ZIKV presented a smaller brain area and cortical plate size compared to the control. Also, embryos from animals facing the co\u2010insult of ZIKV and 2,4D exposition presented higher Caspase 3 positive cells in the cortex, fewer CTIP2+ neurons and proliferative cells at the ventricular zone, and a higher viral load. This phenotype is followed by placental alterations, such as vessel congestion, and apoptosis in the labyrinth and decidua. We also observed a mild spatial correlation between CZS prevalence and 2,4D use in Brazil's North and Central\u2010West regions, with <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.4 and 0.46, respectively. Our results suggest that 2,4D exposition facilitates maternal vertical transmission of ZIKV, exacerbating CZS, possibly contributing to the high prevalence of this syndrome in Brazil's Central\u2010West region compared to other regions.<\/jats:p>","DOI":"10.1002\/tox.24424","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T12:20:58Z","timestamp":1727439658000},"page":"179-190","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prenatal Exposure to Herbicide 2,4\u2010Dichlorophenoxyacetic Acid (2,4<scp>D<\/scp>) Exacerbates Zika Virus Neurotoxicity In Vitro and In Vivo"],"prefix":"10.1002","volume":"40","author":[{"given":"Raissa Rilo","family":"Christoff","sequence":"first","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Universidade Federal do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00e9bora Santos","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratorio de Microbiologia Celular Instituto Oswaldo Cruz, FIOCRUZ  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael Ferreira","family":"Lima","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica, Instituto de Biologia Universidade Federal do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Luiza Meneguci Moreira","family":"Franco","sequence":"additional","affiliation":[{"name":"Laboratorio de Epidemiologia das Malforma\u00e7\u00f5es Cong\u00eanitas Instituto Oswaldo Cruz, FIOCRUZ  Rio de Janeiro Brazil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas (Gen\u00e9tica) Universidade Federal do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiza Mendon\u00e7a","family":"Higa","sequence":"additional","affiliation":[{"name":"Laboratorio de Epidemiologia das Malforma\u00e7\u00f5es Cong\u00eanitas Instituto Oswaldo Cruz, FIOCRUZ  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1tila Duque","family":"Rossi","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica, Instituto de Biologia Universidade Federal do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Batista","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Universidade Federal do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cherley Borba Vieira","family":"de Andrade","sequence":"additional","affiliation":[{"name":"Instituto de Biof\u00edsica Carlos Chaga Filho Universidade Federal do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania Maria","family":"Ortiga\u2010Carvalho","sequence":"additional","affiliation":[{"name":"Instituto de Biof\u00edsica Carlos Chaga Filho Universidade Federal do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas","family":"Ascari","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular e Estrutural (LaBiME), Faculdade de Farm\u00e1cia Universidade Federal do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1rbara","family":"de Azevedo Abrahim\u2010Vieira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Modelagem Molecular &amp; 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