Neurobehavioural Toxicity of Bisphenol S in zebrafish (Danio rerio)
Elevated levels of contaminants from anthropogenic activities are a pernicious problem in various ecosystems. The presence of bisphenol analogues and especially bisphenol S (BPS) in the aquatic environment has been a growing issue of concern over the past few years. BPS concentrations in surface water range from <1- 65600 ng/L. Although these concentrations are much lower than the levels of BPS that cause acute toxicity, the sub-lethal effects of this exogenous compound under chronic exposure remain largely unknown. My thesis addressed this knowledge gap by evaluating how chronic exposure to three different field-relevant concentrations of BPS impact non-reproductive behaviours in zebrafish (Danio rerio). Furthermore, I investigated the possible molecular mechanisms underlying the intragenerational and transgenerational neurobehavioural effects of BPS. To this end, adult male and female zebrafish were exposed to either 1, 10, 30 µg/L BPS or 1 µg/L E2 as a positive control for 75 days. Subsequently, shoal cohesion, excursion from the shoals, group preferences, locomotor activity, anxiety and fear responses were assessed. The results suggest that environmentally relevant concentrations of BPS significantly reduced zebrafish sociality, anxiety and dysregulate the fear responses in adult male and female zebrafish. In the first data chapter, I found that exposure of adult zebrafish to all concentrations of BPS or E2 caused a marked decline in male and female group preference. Meanwhile, locomotor responses and the number of excursions from shoals did not change, and shoal cohesion was only decreased at the highest concentrations of BPS (30 µg/L) and E2. Similarly, in the second data chapter, I documented that 30 µg/L BPS and E2 induced a significant decrease in fear-related responses. At the same time, BPS, irrespective of exposure concentrations, and E2 significantly decreased bottom-dwelling behaviour in both male and female fish. The impaired behavioural responses were associated with a sex-specific dysregulation in the transcription of the neuropeptide signalling system, including isotocinergic and vasotocinergic neuro-endocrine systems, as well as a down-regulation in the transcription of enzymatic antioxidant genes (gpx1a, Cu/Zn-sod, Mn-sod, cat) in the brain of male and female adult zebrafish. In my final experiment, I exposed female zebrafish to various concentrations of BPS and E2 and afterwards bred them with untreated male zebrafish so as to investigate the transgenerational maternal effects of BPS on social behaviours and anxiety responses in offspring. Chronic maternal exposure to BPS (60 days) resulted in alteration in social behaviours and anxiety responses of male offspring in a dose-specific manner likely through oxidative stress and changes in the neuropeptide signalling system. These novel findings expand our current knowledge of the transgenerational effects of BPS, which has been quite limited to date. In summary, this thesis has made significant contributions to identifying the neurobehavioural consequences of chronic exposure to environmentally relevant BPS levels in fish.
Bisphenol S, behaviour, oxidative stress, neuropeptides
Doctor of Philosophy (Ph.D.)