Polygonatum sibiricum polysaccharides mitigate bisphenol S-induced thyroid endocrine disruption and neurodevelopment toxicity in zebrafish larvae

Bisphenol S (BPS) is an emerging environmental endocrine disruptor with increasing ecological and health concerns. This study investigated the effects of BPS on thyroid endocrine function, neurodevelopment, and visual system development in zebrafish larvae, and evaluated the protective potential of Polygonatum sibiricum polysaccharides (PSP). Zebrafish embryos were exposed to environmentally relevant concentrations of BPS alone or in combination with PSP until 120 h post-fertilization. BPS exposure significantly disrupted thyroid hormone homeostasis, altered the expression of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis, and induced neurobehavioral abnormalities and visual impairment. Transcriptomic analysis revealed that BPS markedly disturbed metabolic pathways, particularly tyrosine and retinol metabolism. We further evaluated multi-level biomarker alterations following BPS exposure. Our results revealed imbalances in monoaminergic neurotransmitters, impaired locomotor behaviour, and ocular defects-specifically reduced eye size and retinal thinning-which were accompanied by the downregulation of genes essential for retinal development and photoreceptor function. However, addition of PSP could effectively modulate BPS-induced endocrine disruption, restore neurochemical balance, and prevent BPS-induced behavioral and retinal impairments. Collectively, our findings demonstrate that BPS induces multi-level endocrine and neuro-ocular toxicity by disrupting the HPT axis and tyrosine-retinol metabolism, whereas PSP supplementation effectively mitigates these impairments and restores physiological homeostasis.