Exposure to ZnO nanoparticles alters neuronal and vascular development in zebrafish: Acute and transgenerational effects mitigated with dissolved organic matter. (November 2018) - Kteeba, Shimaa M.
Abstract: Exposure to ZnO-nanoparticles (NPs) in embryonic zebrafish reduces hatching rates which can be mitigated with dissolved organic material (DOM). Although hatching rate can be a reliable indicator of toxicity and DOM mitigation potential, a fish that has been exposed to ZnO-NPs or any other toxicant may also exhibit other abnormal phenotypes not readily detected by the unaided eye. In this study, we moved beyond hatching rate analysis to investigate the consequences of ZnO-NPs exposure on the nervous and vascular systems in developing zebrafish. Zebrafish exposed to ZnO-NPs (1–100 ppm) exhibited an array of cellular phenotypes including: abnormal secondary motoneuron (SMN) axonal projections, abnormal dorsal root ganglion development and abnormal blood vessel development. Dissolved Zn (<10 kDa) exposure also caused abnormal SMN axonal projections, but to a lesser extent than ZnO-NPs. The ZnO-NPs-induced abnormal phenotypes were reversed in embryos concurrently exposed with various types of DOM. In these acute mitigation exposure experiments, humic acid and carbohydrate, along with natural organic matter obtained from the Suwannee River in Georgia and Milwaukee River in Wisconsin, were the best mitigators of ZnO-NPs-induced motoneuron toxicity at 96 h post fertilization. Further experiments were performed to determine if the ZnO-NPs-induced, abnormal axonal phenotypes and the DOM mitigated axonal phenotypes could persist across generations. Abnormal SMN axon phenotypes caused by ZnO-NPs-exposure were detected in F1 and F2 generations. These are fish that have not been directly exposed to ZnO-NPs. Fish mitigated with DOM during the acute exposure (F0 generation) had a reduction in abnormal motoneuron axon errors in larvae of subsequent generations. Therefore, ZnO-NPs exposure results in neurotoxicity in developing zebrafish which can persist from one generation to the next. Mitigation with DOM can reverse the abnormal phenotypes in an acute embryonic exposure context, as well as across generations, resulting in healthy fish. Graphical abstract: Image 1 Highlights: ZnO-NPs exposure in embryonic zebrafish alters neuronal and vascular development. For secondary motoneurons (SMN)s, ZnO-NPs exposure primarily affects dorsal axons. Dissolved Zn exposure affects SMN axons, but to a lesser extent than ZnO-NPs. SMN axon phenotypes caused by ZnO-NPs exposure can persist across generations. DOM can reverse the abnormal SMN phenotypes caused by ZnO-NPs exposure. Abstract : Exposure to ZnO-NPs during zebrafish embryogenesis alters nervous and vascular system development. The nervous system effects can persist across generations and be mitigated by co-exposure to DOM.