Transcriptomic analysis of zebrafish (Danio rerio) liver exposed to sediments from the Loa River

Metal(loid) contamination in aquatic ecosystems, particularly the Loa River in Chile, poses significant environmental and health challenges. This study investigated the molecular impacts of such contamination by exposing zebrafish (Danio rerio) to sediments from pre-impact and severely impacted zones of the Loa River, utilizing transcriptomic analysis of zebrafish liver. Sediment characterization confirmed arsenic as the main driver of contamination, with As concentrations significantly higher at La Finca. Our findings reveal a clear and distinct cascade of molecular responses in fish exposed to impacted sediments, which provides evidence for an Adverse Outcome Pathway. This AOP commences with Molecular Initiating Events, including significant differential expression of genes related to metal adsorption and homeostasis (slc31a1, slc40a1; FDR-adjusted q < 0.05; p < 0.05 for IT7 vs C0 and IT7 vs PIT7), signifying direct perturbations in intracellular metal regulation. This is followed by Key Events characterized by heightened cellular stress, evidenced by significant upregulation of xbp1, xbp1a, xbp1b, and hsp90a/hspd1 (IT7 vs C0; p < 0.05), consistent with oxidative stress and endoplasmic reticulum dysfunction, as well as hypoxia-like conditions. Progressing further, significant differential expression of angiogenesis-related genes (ptprb, mib1, adam10a, foxc1a; p < 0.05) suggests activation of tissue remodeling processes. The cascade culminates in alterations of genes associated with early carcinogenic signaling, including epigenetic regulation (hdac1) and genomic instability (rassf1, top2b; FDR q < 0.05; p < 0.05). This research demonstrates the power of transcriptomics to differentiate the biological impact of contaminated sediments from pre-impact conditions, offering a detailed molecular fingerprint of sublethal effects crucial for identifying early warning signals of environmental degradation and understanding potential human health impacts.