Toxicological Mechanism of the Size–Form Synergy of Nano-Copper Oxide in Danio rerio

CuO-NPs demonstrate significant potential across biomedical, environmental protection, and electronic technology domains. This widespread utilization inevitably leads to their discharge into aquatic ecosystems. Research on the biotoxicity of CuO-NPs constitutes a current scientific priority; however, toxicological impacts related to particle size and morphology remain inadequately documented. The zebrafish (<i>Danio rerio</i> Roloff, 1956) is employed as a model animal organism to assess acute and subchronic toxicity of differentially sized/shaped CuO-NPs. Organ-specific damage manifested in the gills, liver, and muscles. It was found that sheet-shaped CuO-NPs (SC) could induce the most severe histomorphological alterations. Among spherical CuO-NPs (SP), smaller particles exhibited higher toxicity (SC > 40 nm SP-S > 150-250 nm SP-L). Tissue antioxidant capacity followed the same decreasing trend. The three CuO-NPs in the present study reduced microbial alpha-diversity. Altered relative abundance of dominant taxa is observed at the phylum and genus levels. These results expand toxicological datasets for nanomaterial-vertebrate interactions and support environmental risk assessment for nano-pollutants in natural conditions.