Lipidomic and neurobehavioral alterations from developmental lead exposure in zebrafish

Lead (Pb) exposure during early development remains a major public health concern, with no identified safe threshold for developmental neurotoxicity. This study examined the effects of embryonic Pb exposure at environmentally relevant low concentrations (0.01, 0.1, and 1 ppb; µg/L) on neurodevelopmental outcomes in zebrafish (Danio rerio). Embryos were exposed during embryogenesis from 1 to 72 h post-fertilization (hpf), and larval zebrafish were evaluated for cognitive and behavioral performance, oxidative stress biomarkers, lipidomic alterations, and general developmental parameters. Pb-exposed larvae displayed significant cognitive impairments and anxiolytic-like behaviors, along with concentration-dependent disruptions in decision-making behaviors involving complex neural circuits. Developmental outcomes included altered spontaneous movement and heart rate variability. Biochemical assays revealed disrupted estradiol concentrations, late and improper modulation of antioxidant enzyme activities, and increased oxidative stress and lipid peroxidation. Lipidomic profiling showed early upregulation of triacylglycerol (TG) and cholesteryl esters (CE), accompanied by downregulation of sphingomyelin (SM) and phosphatidylcholine (PC) at 72 hpf. By 120 hpf, persistent reductions in phosphatidylethanolamine (PE), SM, and PC were observed, suggesting delayed metabolic reprogramming. Together, these results demonstrate even low Pb concentrations impair neurodevelopmental processes, alter lipid metabolism, and disrupt oxidative balance in zebrafish larvae. Importantly, the findings provide evidence of adverse effects below currently recognized exposure limits, underscoring the heightened sensitivity of the developing brain to Pb and raising concern for long-term cognitive and neurodevelopmental consequences in exposed populations.