Propylparaben impairs muscle development in zebrafish via the PI3K-mTOR pathway

Congenital myopathies are genetically inherited muscle disorders that impair muscle function and strength. While primarily linked to genetic mutations, emerging evidence suggests environmental toxins may exacerbate disease progression. Despite its widespread use as a preservative, the impact of propylparaben (PP) remains insufficiently characterized in current research. This study investigates the mechanisms underlying PP-induced muscle toxicity using Tg (-1.9mylpfa: EGFP) zebrafish. Imaging analysis revealed that PP adversely affected early muscle development, impairing fast and slow muscle fibers as well as precursor cells. Behavioral assessments demonstrated reduced spontaneous motor activity in larvae, resulting in decreased total movement distance, speed, acceleration, and overall activity levels. Mechanistic studies via qPCR and in situ hybridization indicated that PP inhibited the expression of myogenic differentiation factor (MyoD) and myogenic factor 5 (Myf5). Furthermore, PP suppressed the PI3K-mTOR signaling pathway, inhibited muscle cell proliferation, and triggered reactive oxygen species (ROS) accumulation. Notably, co-treatment with mTOR activators (MHY1485 and 3BDO) alleviated PP-induced developmental toxicity and behavioral deficits, confirming PI3K-mTOR pathway inhibition as a key mechanism. This study uncovers the mechanisms underlying PP-induced muscle toxicity, highlighting the interplay between environmental preservatives and genetic susceptibility in congenital myopathies. These findings provide critical insights into how common preservatives may exacerbate muscle-related genetic disorders.