Co-exposure to octocrylene and polystyrene nanoplastics induces neuro- and reproductive toxicity in zebrafish: Association with circadian rhythm and HPG axis disruption

Octocrylene (OC) is a widely used ultraviolet filter frequently detected in aquatic environments. Micro- and nanoplastics (M/NPs) are persistent pollutants that can adsorb organic contaminants such as OC, leading to combined exposure risks. However, the long-term neuroendocrine effects of environmentally relevant co-exposure to OC and nanoplastics remain poorly understood. In this study, adult zebrafish were exposed to OC (5 µg/L) with or without polystyrene nanoplastics (PS-NPs, 80 nm, 1.0 mg/L) for 28 days. Co-exposure to OC and PS-NPs significantly disrupted behavioral phenotypes, suppressed bdnf transcription, and downregulated core circadian clock genes (per1b, per2, per3, cry1a, cry2, nr1d1), indicating aggravated neurotoxicity. Furthermore, co-exposure interfered with sex hormone synthesis and caused gonadal damage by modulating the hypothalamic-pituitary-gonadal (HPG) axis at the transcriptional level, leading to more severe reproductive toxicity and impaired offspring development. Molecular docking revealed that OC may directly interact with estrogen receptors (ERα, ERβ) and CYP19, providing a molecular basis for endocrine disruption. These findings demonstrate that PS-NPs enhance the neurotoxic and reproductive effects of OC through circadian and HPG axis disruption, highlighting the need for considering nanoplastics as toxicity amplifiers in environmental risk assessment.