Detalle de: Unraveling Tributyltin Early Toxicity in Zebrafish Embryos via Lipidomic-Guided Multi-Omics

Tributyltin (TBT) is an organotin compound widely recognized for its severe environmental impacts as an endocrine disruptor, particularly for its obesogenic activity. However, its toxic molecular mechanisms remain incompletely understood, especially during early vertebrate development. Novel multi-omics approaches help address this complexity and improve the characterization of pollutants’ mechanisms of action. Here, we applied an integrative multi-omics strategy combining untargeted lipidomics and transcriptomics to characterize short term (24 h) TBT-induced dysregulation in zebrafish eleutheroembryos at environmentally relevant, sublethal concentrations. Such short-term exposure was sufficient to disrupt lipid homeostasis, oxidative balance, and neurofunction, suggesting that aquatic organisms are far more sensitive to TBT than previously recognized. Lipidomics revealed a general depletion of fatty acids, sterols, and glycerophospholipids, together with an accumulation of glycerolipids, consistent with an obesogenic response. These lipid shifts were supported by transcriptomic changes that highlighted lipid-related hub genes explaining the observed abundance patterns. Moreover, gene expression dysregulation was consistent with epigenomics and transcriptomics data from longer exposure window (2–5 dpf), underscoring the robustness of early TBT alterations on lipid homeostasis, in addition to other RXR-related processes such as neurotoxicity and signaling disruption. These molecular alterations were functionally supported by behavioural impairments, and monoaminergic neurotransmitter disruption.This study demonstrate that TBT induces robust and conserved molecular alterations at early developmental stages, even when exposed only for 24h at environmentally relevant concentrations, with key impacts on lipid homeostasis, oxidative balance, and neurofunction. Therefore, this work highlights the potential of lipidomic-guided multi-omics integration approaches for characterizing and identifying mechanistic pathways affected by endocrine disruptors beyond classical assays.