Phenotypic and transcriptomic effects of developmental exposure to nanomolar levels of pesticides in zebrafish

• All three pesticides exert phenotypic responses below 1nM. • Pesticide exposure led to dose dependent transcriptomic changes. • Pesticide exposure caused non-monotonic behavioral changes. • Pesticide exposure led to changes in cancer, endocrine, and neurological pathways. This study investigates the pesticides atrazine, chlorpyrifos, and dieldrin for endocrine disrupting, phenotypic, and neurobehavioral effects. Zebrafish embryos were exposed to various environmentally relevant concentrations of pesticides during two critical windows, 0-5 days post fertilization (dpf) throughout embryogenesis and 4-5 dpf at early larval development. The toxicity of each chemical and concentration was then determined by evaluating developmental abnormalities, behavioral alterations, and transcriptomic changes. We found the most significant outcomes resulted from dieldrin exposures as low as 1 nM at 0-5 dpf, or 0.1 nM at 4 − 5 dpf, including abnormalities in skeleton, swim bladder, and yolk sec, as well as hyperactive behavioral phenotypes. Following dieldrin exposures at higher concentrations, 100 nM at 0-5 dpf and 1000 nM at 4 − 5 dpf, we observed startle movements at the transition between light and dark stimulus. The transcriptomic changes of high-level dieldrin exposures (1000 nM) implicated movement or seizure disorders. Atrazine at concentrations equal or above 100 nM led to underinflated swim bladders following exposure at 0-5 dpf. Both atrazine exposure paradigms showed transcriptomic changes related to neurological disorders and breast cancer. All chlorpyrifos exposures showed no significant morphological abnormalities and the fewest differentially expressed genes, suggesting chlorpyrifos at 0.01-100 nM exhibited the lowest toxicity among these three pesticides.