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PRENATAL EXPOSURE TO HERBICIDE 2,4-DICHLOROPHENOXYACETIC ACID (2,4D) EXACERBATES ZIKA VIRUS NEUROTOXICITY IN VITRO AND IN VIVO
Produção científica do Laboratório de Microbiologia Celular.
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Abstract
Zika virus (ZIKV) infection during pregnancy can lead to a set of congenital malformations known as Congenital ZIKV syndrome (CZS), whose main feature is microcephaly. The geographic distribution of CZS in Brazil during the 2015–2017 outbreak was asymmetrical, with a higher prevalence in the Northeast and Central-West regions of the country, despite the ubiquitous distribution of the vector Aedes aegypti, 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-N-AS cells to the 15 frequently used agrochemical molecules or derivative metabolites able to cross the blood–brain barrier. We found that a derived metabolite from a widely used herbicide in the Central-West region, 2,4-dichlorophenoxyacetic 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 mg/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-insult 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-West regions, with R² = 0.4 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-West region compared to other regions.
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Wiley
Citation
CHRISTOFF, Raissa Rilo et al. Prenatal exposure to herbicide 2,4-dichlorophenoxyacetic acid (2,4D) exacerbates Zika virus neurotoxicity in vitro and in vivo. Environmental Toxicology, p. 1-12, 27 Sept. 2024.DOI
10.1002/tox.24424ISSN
1520-4081Notes
Produção científica do Laboratório de Epidemiologia de Malformações Congênitas.Produção científica do Laboratório de Microbiologia Celular.
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