Lipophagy suppression: a novel mechanism for developmental disruption by nanoplastics/MC-LR in zebrafish

The coexistence of nanoplastics (NPs) with environmental pollutants has raised growing ecological concern. To investigate the effects of polystyrene nanoplastics (PSNPs) and microcystin-LR (MC-LR) on early development, zebrafish embryos were exposed to PSNPs and/or MC-LR from fertilization through 7 days post-fertilization. The exposure groups included MC-LR alone (0, 1, 5, and 20 μg/L) and a combined exposure group of PSNPs (10 mg/L) with MC-LR. Both individual and combined exposures disrupted zebrafish early development and growth, with co-exposure notably exacerbating lipid accumulation. Metabolomic profiling revealed significant disruptions in lipid metabolic pathways under combined exposure. Mechanistically, co-exposure of PSNPs and MC-LR increased intracellular reactive oxygen species (ROS), induced endoplasmic reticulum stress (ERS), and inhibited lipophagy, leading to lipid accumulation. Developmental toxicity also manifested as skeletal malformations, linked to suppressed BMP signaling pathway. Moreover, MC-LR enhanced the in vivo accumulation of PSNPs, likely via strong binding of PSNPs with MC-LR followed by the interaction of MC-LR and PP2A, as supported by molecular docking and dynamic simulations. These results underscore the potential ecological risks of co-exposure to nanoplastics and algal toxins during early vertebrate development. In summary, our study demonstrates that PSNPs, by adsorbing MC-LR, accumulate excessively in zebrafish, thereby inducing elevated ROS levels, activation of ERS, impairing lipid homeostasis, and causing developmental abnormalities during early life stages. These findings highlight the potential hazards of MC-LR and PSNP co-existence for early fish development and underscore the broader ecological risks posed to aquatic ecosystems.