Metabolic characterizations of PFOS-induced disruptions in early embryonic development

Perfluorooctane sulfonates (PFOS) are persistent environmental pollutants linked to developmental toxicity, but the mechanisms remain unclear. This study investigates the metabolic changes induced by PFOS exposure during early embryonic development and integrates metabolomic, transcriptomic, and molecular docking analyses to explore underlying mechanisms.

Mouse embryoid bodies (mEBs) were exposed to PFOS for 2 days, 4 days and 6 days. Metabolomic profiling was conducted to identify differential metabolites. Transcriptomic data were integrated with metabolomics using Cytoscape to map metabolic pathway alterations. Molecular docking simulations were performed to assess PFOS binding to key enzymes.

PFOS exposure resulted in significant alterations in lipid (Erucic acid, L-carnitine), amino acid (L-methionine, creatine, hippuric acid, and spermine), and nucleotide metabolism (e.g., hypoxanthine). Integrated transcriptomic and metabolomic analysis revealed disrupted pathways included SLC25A20 regulated L-carnitine metabolism. Molecular docking simulations indicated that PFOS binds to methionine synthase and hypoxanthine guanine phosphoribosyl transferase, potentially inhibiting their function and disrupting metabolic homeostasis for L-methionine and hypoxanthine during embryonic development.

PFOS exposure disrupts key metabolic pathways critical for embryogenesis, including lipid, amino acid, and nucleotide metabolism. Molecular docking and transcriptomic integration highlight enzyme targeting as a potential mechanism of PFOS-induced developmental toxicity. These findings provide novel insights into the molecular and metabolic disruptions caused by PFOS, with implications for understanding its developmental toxicity.