Integrated transcriptomic and metabolomic analysis reveals the molecular mechanisms underlying perfluorooctanoic acid (PFOA)-induced developmental toxicity during the early life stages of Paralichthys olivaceus.

Perfluorooctanoic acid (PFOA) is a representative persistent organic pollutant widely present in the marine environment. However, its toxicological mechanisms during early developmental stages in marine benthic fish are not yet fully understood. In this study, the embryos and larvae of Paralichthys olivaceus were employed to investigate the toxic effects of PFOA during early development using a multi-omics approach. A 96-h acute exposure experiment was conducted, involving six exposure concentrations: 0 (control group), 5, 10, 20, 50, and 100 mg/L. The results revealed that the PFOA concentrations of 50 and 100 mg/L significantly decreased hatching rates and induced developmental abnormalities. The average cumulative mortality and malformation rates of the treatment groups at these two concentrations reached 47.13% and 29.27%, respectively, which were 3.9 and 2.5 times those of the control group. Transcriptomic analysis identified 1272, 2500, and 2155 differentially expressed genes (DEGs) in the 5, 20, and 100 mg/L exposure groups, respectively, relative to the control group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that these DEGs were significantly enriched in pathways associated with retinol metabolism, drug metabolism by other enzymes, drug metabolism via cytochrome P450, and xenobiotic metabolism via cytochrome P450. Metabolomic analysis identified 95, 165, and 163 differentially altered metabolites in the 5, 20, and 100 mg/L PFOA exposure groups, respectively, compared to the control group. KEGG enrichment analysis further indicated that 11 metabolic pathways were significantly affected, including nucleotide metabolism, purine metabolism, and pyrimidine metabolism. Integrated transcriptomic and metabolomic analysis revealed that PFOA-induced embryotoxicity is associated with disruption of nucleotide and pyrimidine metabolism. These findings suggest that PFOA induces embryotoxicity through targeted disruption of fundamental developmental processes-specifically, the coordinated regulation of cell proliferation and de novo nucleic acid synthesis. This mechanistically anchored evidence establishes a robust, experimentally derived acute toxicity benchmark for P. olivaceus, and delivers the first species-specific molecular framework for understanding PFOA's developmental mode of action in marine benthic teleosts.