Zearalenone delays tissue regeneration by dysregulating neutrophil balance in zebrafish (Danio rerio) larvae.

Abstract

Zearalenone (ZEA), a common mycotoxin, poses significant environmental and health risks. While its toxicological effects are well-studied, its impact on regeneration remains unclear. This study explored ZEA's effects on zebrafish (Danio rerio) larvae, focusing on developmental toxicity, immunotoxicity, and tissue regeneration. Embryos were exposed to 0, 0.5, 1, and 1.5 μM ZEA from 6 to 72 h post-fertilization (hpf). Although hatching and survival rates remained unaffected, malformations, including body axis bending and pericardial edema, increased dose-dependently, with 4.44 % abnormalities observed at 1.5 μM (p = 0.01). Heart rates also declined significantly at 1.5 μM (75.40 vs. 72.53 beats/30s, p = 0.0054). Immunotoxicity was assessed using Tg(mpx: eGFP) zebrafish to monitor neutrophil responses post-injury. ZEA exposure led to increased neutrophil counts (229.87 vs. 330.80, p < 0.0001) and chemotaxis (21.15 % vs. 34.57 %, p < 0.0001). RNA sequencing of 0 and 1.5 μM groups revealed disrupted redox balance and oxygen transport, with down-regulation of hbae1, hbbe2, and hbae3 and up-regulation of hif1a, indicating hypoxia involvement. Elevated reactive oxygen species (ROS), reduced antioxidant enzyme activity, and increased apoptosis were also observed. Tail fin regeneration assays showed delayed regeneration at 1 and 1.5 μM ZEA, linked to impaired immune function and oxidative stress. These findings highlight ZEA's adverse effects on developmental and regenerative processes, underscoring its environmental and health implications and the need for further research.