From cradle to grave: Deciphering sex-specific disruptions of the nervous and reproductive systems through interactions of 4-methylbenzylidene camphor and nanoplastics in adult zebrafish

4-methylbenzylidene camphor (4-MBC) and micro/nanoplastics (MNPs) are common in personal care and cosmetic products (PCCPs) and consumer goods; however, they have become pervasive environmental contaminants. MNPs serve as carriers of 4-MBC in both PCCPs and the environment. Our previous study demonstrated that 4-MBC induces estrogenic effects in zebrafish larvae. However, knowledge gaps remain regarding the sex- and tissue-specific accumulation and potential toxicities of chronic coexposure to 4-MBC and MNPs. Herein, adult zebrafish were exposed to environmentally realistic concentrations of 4-MBC (0, 0.4832, and 4,832 μg/L), with or without polystyrene nanoplastics (PS-NPs; 50 nm, 1.0 mg/L) for 21 days. Sex-specific accumulation was observed, with higher concentrations in female brains, while males exhibited comparable accumulation in the liver, testes, and brain. Coexposure to PS-NPs intensified the 4-MBC burden in all tested tissues. Dual-omics analysis (transcriptomics and proteomics) revealed dysfunctions in neuronal differentiation, death, and reproduction. 4-MBC-co-PS-NP exposure disrupted the brain histopathology more severely than exposure to 4-MBC alone, inducing sex-specific neurotoxicity and reproductive disruptions. Female zebrafish exhibited autism spectrum disorder-like behavior and disruption of vitellogenesis and oocyte maturation, while male zebrafish showed Parkinson's-like behavior and spermatogenesis disruption. Our findings highlight that PS-NPs enhance tissue accumulation of 4-MBC, leading to sex-specific impairments in the nervous and reproductive systems of zebrafish. Micro/nanoplastics (MNPs), along with the UV filter 4-methylbenzylidene camphor (4-MBC), are consistently released into aquatic ecosystems, presenting potential risks to both wildlife and human. In addition to their inherent characteristics, MNPs act as carriers for 4-MBC in both personal care and cosmetic products and the environment, raising concerns about their status as emerging environmental pollutants. The long-term toxicity of lower concentrations of 4-MBC and MNPs and their subsequent impact on aquatic organisms are not yet fully understood. This study aims to deepen our understanding of the role of nanoplastics in exacerbating the neurotoxic and reproductive effects of 4-MBC within ecosystems.