Abstract
Although the zika virus (ZIKV) has now been strongly correlated with emerging cases of microcephaly in the Americas, suspicions have been raised regarding the use of pyriproxyfen, a larvicide that prevents mosquito development, in drinking water. The effects of this compound on neurodevelopment have not yet been addressed specifically in vertebrates. As a result, we aimed at addressing the effects, if any, of pyriproxyfen on neurodevelopment in the zebrafish embryo as a vertebrate model. Using zebrafish transgenic lines expressing GFP in different cell populations (elavl3 in newborn neurons, gfap and nestin in neural stem cells), we focused on the analysis of whole embryonic brain volume after confocal 3D-reconstruction and the quantification of purified neural stem cells during early neurodevelopment by FACS-cell sorting from whole in vivo embryos. Interestingly, though lethal at very high doses, pyriproxyfen did not cause brain malformation nor any significant changes in the number of observed stem cells in the developing central nervous system. Our data indicate that pyriproxyfen does not affect central nervous system development in zebrafish, suggesting that this larvicide on its own, may not be correlated with the increase in microcephaly cases reported recently.
Highlights
The zika virus (ZIKV) has been strongly correlated with emerging cases of microcephaly in the Americas, suspicions have been raised regarding the use of pyriproxyfen, a larvicide that prevents mosquito development, in drinking water
The incidence of reported microcephaly cases has vastly increased in the Americas since the rapid emergence of the Zika virus (ZIKV), a flavivirus related to dengue, West Nile and yellow fever viruses[1,2,3]
Pyriproxyfen has been recently brought into the public eye following an intense debate involving anecdotal claims that it may potentially be the cause of the surge of microcephaly cases reported in the Americas, as it is commonly used in drinking water as a mosquito growth-inhibitor
Summary
The zika virus (ZIKV) has been strongly correlated with emerging cases of microcephaly in the Americas, suspicions have been raised regarding the use of pyriproxyfen, a larvicide that prevents mosquito development, in drinking water The effects of this compound on neurodevelopment have not yet been addressed in vertebrates. Depending on the severity of the microcephaly, affected children may present with developmental delays, difficulty with motor coordination, facial distortions, seizures and mental retardation[6] This condition can be caused by a variety of genetic and environmental factors such as craniosynostosis, chromosomal abnormalities, decreased oxygen to the fetal brain, exposure to drugs or alcohol during pregnancy, malnutrition, uncontrolled maternal phenylketonuria or diabetes as well as infections of the fetus during pregnancy[7,8,9,10,11,12]. Many questions remain regarding the transmission of the virus and its role in microcephaly, but studies examining fetuses and infants with microcephaly have shown the presence of ZIKV RNA in the placenta, amniotic fluid and fetal tissues and have shown the presence of the virus in brain tissues, suggesting it plays a role in the development of this condition[16,17]
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