O-phenylphenol induces cardiac injury by regulating cardiac progenitor cells in zebrafish (Danio rerio).

O-phenylphenol (OPP) is a widely used environmental contaminant, but its potential toxic effects on vertebrate cardiovascular development remain poorly understood. This study systematically evaluated OPP's developmental and cardiotoxic effects using zebrafish models, combining embryological exposure (0-9 mg/L, 5-72 h post-fertilization) with adult chronic exposure (0-4 mg/L, 30 days). Embryonic assessments combined morphological analysis, in situ hybridization, transcriptomics, and molecular pathway characterization, while adult chronic exposure studies focused on histological and functional cardiac evaluations. Our findings demonstrated that embryonic OPP exposure induced dose-dependent developmental toxicity, including reduced body length, yolk sac expansion, and cardiac malformations ranging from mild (heart linearization) to severe (cardia bifida). In situ hybridization confirmed that cardia bifida hearts possessed independent atrial and ventricular chambers. Mechanistically, OPP inhibited cardiac progenitor cell migration and suppressed the expression of migration-related genes (gata4, snai1a). OPP exposure also inhibited ATPase activity, resulting in impaired cardiac function, as demonstrated by reduced cardiac output and decreased heart rate. Furthermore, transcriptomic analysis revealed concomitant dysregulation of calcium signaling and cardiac muscle contraction pathways. Adult exposure induced myocardial fiber dissolution and cardiomyocyte nuclear enlargement. These findings demonstrate that OPP compromises cardiac development through progenitor cell migration defects and impairs cardiac function via ATPase inhibition and calcium signaling disruption. This study provides valuable insights into the potential cardiotoxic risks associated with environmental toxins.