Transcriptomic analysis reveals neurobehavioral impairment in zebrafish during early life following environmentally relevant exposure to short-chain chlorinated paraffins.

Short-chain chlorinated paraffins (SCCPs), an emerging class of persistent organic pollutants (POPs), may pose neurotoxic risks; however, current evidence remains limited. This study aimed to investigate the developmental and neurobehavioral effects of early-life SCCPs exposure in zebrafish larvae, as well as the underlying potential mechanisms. Wild-type zebrafish embryos were exposed to short-chain chlorinated paraffins (SCCPs; C10-13, 63% chlorine) at 0, 0.2, 2, 20, and 200 μg/L from 2 to 120 h post fertilization. Developmental, morphological, and behavioral endpoints were evaluated, and SCCP accumulation was quantified using UPLC-Q-Exactive Orbitrap MS. Transcriptomic profiling was conducted by QuantSeq sequencing, followed by GO and KEGG enrichment analyses. Differential gene expression was validated by Quantitative real-time PCR (qRT-PCR). No significant effects of SCCPs on zebrafish embryonic development were observed. However, larval exposure to SCCPs markedly reduced swimming speed and distance in a concentration-dependent manner. Accumulation of SCCPs in zebrafish larvae increased with higher exposure concentrations. Transcriptomic profiling identified 1542 differentially expressed genes, which were predominantly enriched in pathways related to neurotransmitter receptor and synaptic function. Gene Set Enrichment Analysis (GSEA) revealed significant downregulation of gene sets related to the GABA receptor complex and neuroactive ligand-receptor interactions. qRT-PCR analysis further confirmed the downregulation of key neurodevelopmental genes (elavl4, gria1b, gria2b, gria4b) following SCCPs exposure. In conclusion, early life exposure to SCCPs reduced locomotor activity in zebrafish larvae, likely mediated by the inhibition of neurotransmitter receptor function.