Effects of exposure to environmental pollutants on neural and skeletal development in the zebrafish embryo model

Environmental pollution is a serious emerging global issue, threatening human and environmental health. Chemicals and waste products alter the natural equilibrium of our surroundings, and organisms including humans are inevitably exposed. A growing field in research is dedicated to defining the entity and modality of exposure to contaminants, and the consequences on the ecosystem and on human health. While epidemiological studies are applied on humans, experimental research on these issues increasingly use Zebrafish embryos as an ideal animal model. With these, it is possible to quantify the potential toxicity/teratogenicity or the interference with physiological functions in relation with exposure to specific external substances. In this thesis I aim to provide some examples of neural and morphologic alteration on zebrafish embryos due to exposure to environmental pollutants, by behavioural and transcriptomic analyses. BPA is a monomer widely used as plasticizer, proven to be an endocrine-disrupting compound (EDC). A recent article shows a disrupting effect of this molecule on the development of pharyngeal cartilages, due to perturbed estrogen-mediated signalling. This adverse effect has been observed both in exposed individuals (F0) and in their offspring (F1), indicating epigenetic inheritance. Additionally, BPA exposure also results in altered hatchability and heart rate, depending on the exposure concentration. RNA-seq profiling shows differentially expressed genes related to cartilage and bone development, strongly supporting the adverse action of BPA on skeletal development. Another study focuses on the effect of 2, 2′, 4, 4′-tetrabromodiphenyl ether (BDE-47), commonly used as flame-retardant. The authors measured the neurodevelopmental toxicity of BDE-47 using a combination of behavioural assessment and transcription profiling following a 7 days-long exposure to BDE-47 and high-intensity light - embryos photomotor response inducer. The treated group shows lower hatching rate, higher mortality and altered heart rates. The difference between treated and untreated embryos increases as the exposure time increases. At the biochemical level, the pathways for Hedgehog, FoxO, Toll-like receptor and Steroid biosynthesis were found to be dysregulated. Silica nanoparticles (NPs) derive from plastic degradation and contaminate nearly all environmental systems. The adverse effects of NPs on the environment and on human health is still poorly understood. They have been found to cause neurotoxic effects depending on their size and on the variable charge. NPs have also been shown to induce oxidative stress in cells and cause cytoskeleton defects. Indeed, it has been proposed that NPs may exacerbates the potential risks of chemical contaminants, including EDCs. Zebrafish embryos were treated with environmentally relevant doses of NPs, then examined for their morphological features, locomotor response profile (LMP), light/dark challenge (LDC) and gene expression by qPCR. The results show: 1) significantly altered morphology; 2) altered locomotor response; 3) altered light/dark motor behaviour profile; 4) altered expression of neurodevelopment and autophagy genes. The observed effects depend on the particle size and concentration. These results confirm the adverse effects of NPs on development and motor physiology of fish embryos. The results provided by these articles confirm the relation between EDC and NPs exposure with morphological defect