Lipidomics Atlas Tracks Alterations Associated with Deltamethrin-Induced Developmental Neurotoxicity in Embryonic Zebrafish

Deltamethrin (DM) is a widely used pyrethroid pesticide associated with childhood neurodevelopmental disorders. However, the specific impact of DM exposure during distinct early life stages remains unclear. Here, zebrafish embryos were exposed to DM at different stages: before (10-16 hpf), at the onset of (16-24 hpf), at the peak of (24-36 hpf) hypothalamic neurogenesis, and continuously from 10 to 120 hpf (subchronic exposure), using different dosages (1, 100, and 250 nM). Exposure to middle/high-dose DM at 24-36 and 10-120 hpf significantly reduced zebrafish locomotor activities and increased apoptotic cells in the spinal cord. As a pivotal factor in central nervous system disorder progression, altered lipid metabolism was investigated using nontargeted lipidomic analysis. DM exposure at 10-16 and 24-36 hpf led to the most significant lipidome reprogramming. Despite exhibiting a dose-dependent trend, even low-dose DM changed the lipidome. Cer 40:2;2 and PG 44:12 showed potential in identifying DM exposure effects. Significant changes in sphingolipid, cardiolipin, phosphatidylglycerol, and glycerolipid pathways were linked to DM-induced developmental neurotoxicity, indicating impaired membrane function, mitochondrial damage, and disrupted energy metabolism. Our study sheds new light on assessing early neurodevelopmental disturbances and identifying intervention targets, emphasizing sensitivity to DM during the critical early phase of neurodevelopment.