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Zinc oxide nanoparticles (ZnO NPs) are commonly used nanomaterials (NMs) with versatile applications from high-end technologies to household products. This pervasive utilisation has brought human in the close interface with nanoparticles (NPs), hence questioning their safety prior to usage is a must. In this study, we have assessed the effects of chronic exposure to ZnO NPs (<50 nm) on the model organism Drosophila melanogaster . Potential toxic effects were studied by evaluating longevity, climbing ability, oxidative stress and DNA fragmentation. Ensuing exposure, the F0 (parent), F1, F2, F3 and F4 generation flies were screened for the aberrant phenotype. Flies exposed to ZnO NPs showed distinctive phenotypic changes, like deformed segmented thorax and single or deformed wing, which were transmitted to the offspring’s in subsequent generations. The unique abnormal phenotype is evident of chronic toxicity induced by ZnO NPs, although appalling, it strongly emphasize the importance to understand NPs toxicity for safer use. [ABSTRACT FROM AUTHOR]

ZnO nanoparticles (ZnO NPs) are widely used engineered nanomaterials. Due to induced genotoxicity, increased oxidative stress, and teratogenicity, these NPs have been reported to be toxic. In the present study, we emphasise the role of vital proteins in regulating ZnO NP-induced abnormal phenotypes, particularly the deformed thorax and single wing in the Drosophila melanogaster progeny fed on 0.1–10 mM ZnO NPs. To understand how protein expression regulates this particular phenotype on ZnO NPs exposure, toxicoproteomics profile of control and abnormal phenotype flies was generated using LC/MS/MS. Gene ontology enrichment studies of proteomics data were carried out using CLUEGO and STRAP software. The bioinformatics tool STRING was used to generate a protein–protein interaction map of key proteins of enrichment analysis. Following ZnO NP exposure, the differential expression of key proteins of the Wnt pathway was prominent. Altered expression of various proteins of the Wnt pathway (CaMKII), cytoskeleton (Actin), and calponin resulted in developmental defects in drosophila progeny. In addition, immunohistology studies showed a significant deviation in the expression of wingless protein of ZnO NPs treated larvae in comparison to control. According to these findings, the interaction of the wnt pathway and cytoskeletal proteins with ZnO NPs caused developmental abnormalities in the subsequent generation of drosophila, highlighting the transgenerational toxic effects of these nanoparticles. [Display omitted] • ZnO NPs alters wnt signaling pathway in Drosophila melanogaster. • Interaction of ZnO NPs with cytoskeleton proteins caused developmental deformities. • Transgenerational toxicity profile of flies shows lethal effects of ZnO NPs. [ABSTRACT FROM AUTHOR]