Metabolomic changes following GenX and PFBS exposure in developing zebrafish

Area of Science:

• Environmental toxicology
• Metabolomics
• Zebrafish models

Background:

• Short-chain per- and polyfluoroalkyl substances (PFAS), including GenX and PFBS, are replacements for persistent long-chain PFAS.
• These emerging contaminants are found globally in water sources.
• Limited data exists on their metabolic effects and toxicity from early-life exposure.

Purpose of the Study:

• To investigate the toxicity and metabolic alterations caused by early-life exposure to GenX and PFBS in larval zebrafish.
• To quantify the uptake of GenX and PFBS in zebrafish larvae.
• To identify specific metabolic pathways affected by these short-chain PFAS.

Main Methods:

• Larval zebrafish were exposed to 150 µM GenX or 95.0 µM PFBS from 4 hours post-fertilization to 6 days post-fertilization.
• Uptake of chemicals was quantified using ultra-high-performance liquid chromatography and high-resolution mass spectrometry.
• Targeted and untargeted metabolomics analyses were performed to assess metabolic changes.

Main Results:

• PFBS uptake was 20.4% higher than GenX in zebrafish larvae.
• PFBS exposure altered 13 targeted metabolites and 21 metabolic pathways; GenX altered 1 metabolite and 17 pathways.
• Both chemicals significantly impacted amino acid metabolism, with PFBS also affecting carbohydrate, lipid, and xenobiotic metabolism.

Conclusions:

• GenX and PFBS exposure significantly alters the zebrafish metabolome.
• Significant dysregulation observed in metabolic pathways crucial for growth and development.
• Findings highlight potential risks associated with early-life exposure to these short-chain PFAS replacements.