Developmental exposure to Bisphenol S causes neurobehavioural deficits in larval zebrafish (Danio rerio)

Bisphenol S (BPS) is a widely used synthetic compound and is known as an endocrine-disrupting chemical (EDC). The ability of BPS to bind predominantly to estrogen receptors raises significant concern, as it can interfere with different neurological functions, leading to neurobehavioural deficits. Despite extensive research documenting various adverse effects of BPS in adult fish, its neurobehavioural effects, especially in early life stages of fish, remain poorly understood. In the present study, zebrafish embryos (4-hours post fertilization, hpf) were exposed to an environmentally relevant concentration of BPS (30 μg/L), in addition to control and DMSO (0.01%; vehicle control), until 120 hpf, followed by behavioural, biochemical, and molecular assessments. BPS exposure impaired tail coiling frequency in embryos (20 hpf), and thigmotaxis and reflexive movement behaviour (120 hpf) in zebrafish larvae. At 120 hpf, larvae showed elevated reactive oxygen species (ROS), increased apoptosis, and higher malondialdehyde (MDA) levels, indicating lipid peroxidation and oxidative damage. Biochemical analysis further demonstrated that BPS significantly increased whole body serotonin (5-HT) and acetylcholine levels at 120 hpf. Moreover, gene expression analysis at 120 hpf indicated that BPS exposure resulted in the dysregulation of genes involved in dopaminergic, serotonergic and cholinergic neurotransmitter pathways, apoptosis pathway, oxidative stress response, and neuroinflammation. These findings suggest that BPS induces oxidative stress, neuroinflammation and apoptosis, leading to the disruption of neural development and signaling pathways involved in regulating behavioural responses. Overall, our study provides new insights into the behavioural effects and underlying neurotoxic mechanisms of developmental BPS exposure in larval zebrafish.