Embryonic exposure to Bisphenol S causes long-term social behavioural alterations in adult zebrafish (Danio rerio)

Bisphenol S (BPS), a widely used substitute for Bisphenol A (BPA), is frequently detected in aquatic environments and has raised concerns due to its potential neurotoxic effects. Despite being marketed as a safer alternative, the long-term impacts of BPS on neural function and behaviour remain poorly understood. This study investigated whether embryonic exposure to environmentally relevant concentrations of BPS induces persistent neurobehavioural, neurochemical, and molecular alterations in adult zebrafish (Danio rerio). Embryos were exposed to an environmentally relevant concentration of BPS (30 µg/L) from 4 to 120 h post-fertilization (hpf) and subsequently reared in clean water until 6 months of age. Adult behavioural assessments revealed that BPS-exposed fish exhibited significant deficits in social affiliation, spending less time in the conspecific zone during group preference testing. However, shoaling behaviour and anxiety-like responses in the novel tank test, including swimming speed and zone preference, remained unaffected. Neurochemical analysis showed a significant reduction in brain dopamine levels, while serotonin (5-HT) and acetylcholine (ACh) levels were unchanged. Oxidative damage was corroborated by a significant elevation of brain lipid peroxidation (LPO) following embryonic BPS exposure. Molecular profiling of adult brain tissues revealed alterations in genes associated with oxidative stress (gpx1a), apoptosis (p53, bax, casp3), neuroinflammation (tnf-α, il1b, ngfb), and neurotransmission, particularly within serotonergic (slc6a4b, htr1d, htr2b) and cholinergic (chata) pathways. These findings indicate that embryonic BPS exposure leads to persistent neurochemical and transcriptional changes that selectively impair adult social behaviour without broadly affecting anxiety or locomotion. These observations underscore the potential neurodevelopmental toxicity of BPS and the urgent need to re-evaluate its safety in aquatic environments.