Environmental antibiotics in wastewater disrupt zebrafish embryonic development via Wnt/β-catenin signaling: mechanistic insights and implications for risk assessment

Antibiotic residues in wastewater treatment plant (WWTP) effluents are a matter of global environmental health concern. This study combined global WWTP monitoring data with epidemiological modeling and zebrafish embryo assays to assess developmental risks. A meta-analysis of 121 studies identified amoxicillin, trimethoprim and norfloxacin as high priority contaminants. Ecological modeling using generalized additive models (GAM) revealed a statistical association between effluent antibiotic levels and neonatal disease incidence. Zebrafish exposed to environmentally relevant concentrations exhibited dose-dependent developmental toxicity, including pericardial edema, oxidative stress, and impaired cardiac function. Molecular analysis indicated dysregulation of the Wnt/β-catenin signaling pathway, with Wnt1 upregulation mediating toxic effects. Functional validation using CRISPR interference targeting wnt1 attenuated cardiac malformations and apoptosis, while docking simulations confirmed strong antibiotic–Wnt1 binding. These findings establish a mechanistic link between environmental antibiotic exposure and developmental toxicity and underscore the potential of Wnt1 as a biomarker for ecological risk assessment. This work supports the need for advanced tertiary treatment strategies and molecular-based monitoring frameworks. • Antibiotic pollution in wastewater links to neonatal diseases. • Zebrafish embryos exposed to antibiotics show pericardial edema and oxidative stress. • Antibiotic exposure disrupts Wnt/β-catenin signaling, causing developmental toxicity. • Wnt1 knockdown reduces cardiac malformations and apoptosis in zebrafish embryos.