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Nanoplastics and sunscreens contained in personal care products induce neurotoxicity in early zebrafish embryos

ABSTRACT: Nanoplastics with small particle size and high surface area/volume ratio make them easy to absorb environmental pollutants and affect their bioavailability. In this study, polystyrene nanoplastic beads (PS-NPBs) with a particle size of 100nm and sunscreen butyl methoxydibenzoylmethane (BMDBM) contained in personal care products were chosen as target pollutants to study their developmental toxicity and interactive effects on zebrafish embryo. The exposure period was 2-12 hours post fertilization (hpf). The BMDBM and PS-NPBs significantly upregulated the genes related to antioxidant enzymes and downregulated the gene expression of aromatase and DNA methyltransferases, but the influenced genes were not exactly the same, and the combined exposure reduced the adverse effects on the expression of all genes. With the help of single-cell RNA sequencing technology, the neural mid cells were identified as the target cells of both pollutants, and brain development, head development and notch signaling pathway were the functions they commonly altered. The key genes and functions that are specifically affected by BMDBM and/or PS-NPBs were identified. The BMDBM mainly affect the differentiation and fate of neurons in central nervous system through the regulation of her5, her6, her11, lfng, pax2a and fgfr4. The PS-NPBs regulated the expression of olig2, foxg1a, fzd8b, six3a, rx1, lhx2b, nkx2.1a and sfrp5 to alter nervous system development, retinal development, and stem cell differentiation. The phenotypic responses of zebrafish larvae at 120 hpf were tested, and significant inhibition of locomotor activity was found, indicating that early disrupting effect on central nervous system would have a sustained impact on the behavior of zebrafish.

ORGANISM(S): Danio rerio

PROVIDER: GSE157816 | GEO | 2020/09/12

REPOSITORIES: GEO

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Project description:Congenital malformations are a prevalent cause of infant mortality in the United States and their induction has been linked to a variety of factors, including exposure to teratogens. However, the molecular mechanisms of teratogenicity are not fully understood. MicroRNAs are an important group of small, non-coding RNAs that regulate mRNA expression. MicroRNA roles in early embryonic development are well established, and their disruption during development can cause abnormalities. We hypothesized that developmental exposure to teratogens such as valproic acid alters microRNA expression profiles in developing embryos. Valproic acid is an anticonvulsant and mood-stabilizing drug used to treat epilepsy, bipolar disorder and migraines. To examine the effects of valproic acid on microRNA expression during development, we used zebrafish embryos as a model vertebrate developmental system. Zebrafish embryos were continuously exposed to valproic acid (1 mM) or vehicle control (ethanol) starting from 4 hours post-fertilization (hpf) and sampled at 48 and 96 hpf to determine the miRNA expression profiles prior to and after the onset of developmental defects. At 96 hpf, 95% of the larvae showed skeletal deformities, abnormal swimming behavior, and pericardial effusion. Microarray expression profiling was done using Agilent zebrafish miRNA microarrays. Microarray results revealed changes in miRNA expression at both the time points. Thirteen miRNAs were differentially expressed at 48 hpf and 22 miRNAs were altered at 96 hpf. Among them, six miRNAs (miR-16a, 18c, 122, 132, 457b, and 724) were common to both time points. Bioinformatic target prediction and examination of published literature revealed that these miRNAs target several genes involved in the normal functioning of the central nervous system. These results suggest that the teratogenic effects of valproic acid could involve altered miRNA expression. Small RNA profiles were deteremined in valproic acid exposed zebrafish embryos using Agilent miRNA microarrays

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Nanoplastics and sunscreens contained in personal care products induce neurotoxicity in early zebrafish embryos

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