GSE169579
Next generation sequencing to assess prenatal exposure to aerosols of paraquat and TiO2 nanoparticles on the gene expression of the developing brain
Nanopesticides (NPe) are innovative pesticides involving engineered nanomaterials (ENM) to increase the efficiency of plant protection products. However, no toxicological data is available on their inhalation toxicity and the potential cocktail effects between pesticide active substances and ENM. In particular, the neurodevelopmental toxicity of prenatal repeated exposures has not been specifically evaluated. To this end, C57Bl/6j gestating mice were exposed to aerosols in an ad hoc whole-body exposure chamber. Exposures consisted in low repeated doses of the paraquat herbicide (PQ), and/or TiO2 nanoparticles (nTiO2). The monitoring of aerosol characteristics, in addition to their prior metrological characterization, enabled a precise estimation of the exposure doses received by animals, which can be extrapolated to the recommended exposure limit proposed by health agencies. We used RNA-seq to assess the gene expression in pups striatum at post-natal stage, in order to highlight possible neurodevelopmental alterations. This sensitive method revealed that both PQ and nTiO2 aerosols had a significant effect on the gene expression of the offspring, highlighting dysregulations of oligodendrocyte differentiation and neuronal maturation. Exposure to the nTiO2 aerosol modulated notably the regulation of neurotransmitters pathway being possibly indirect consequences of a minor change in the neuroinflammation state. No synergy was found between the PQ + nTiO2. Instead, the neurodevelopmental effects were surprisingly lower than the one measured for each substance separately. Overall design: Exposure of C57Bl/6J gestating mice to aerosols and assessment of the pups striatum transcriptome at post-natal stage to highlight possible neurodevelopmental alterations