Maternal exposure to bisphenol S reduces anxiety and impairs collective antipredator behavior of male zebrafish (Danio rerio) offspring through dysregulation of their serotonergic system

Bisphenol S (BPS) is a common endocrine-disrupting chemical globally used in several consumer and industrial products. Although previous studies suggested that BPS induces multiple effects in exposed organisms, very little is known about its intergenerational effect on offspring behavior and/or the potential underlying mechanisms. To this end, adult female zebrafish Danio rerio were exposed to BPS (0, 10, 30 mu g/L) and 1 mu g/L of 17-beta-estradiol (E2) as a positive control for 60 days. Afterwards, female fish were bred with untreated males, and their offspring were raised to 6 months old in control water. Maternal exposure to BPS decreased male offspring anxiety and antipredator behaviors while boldness remained unaffected. Specifically, maternal exposure to 10 and 30 mu g/L BPS and 1 mu g/L E2 were found to impact male offspring anxiety levels as they decreased the total time that individuals spent in the dark zone in the light/dark box test and increased the total track length in the center of the open field test. In addition, maternal exposure to all concentrations of BPS and E2 disrupted antipredator responses of male offspring by decreasing shoal cohesion in the presence of chemical alarm cues derived from conspecifics, which communicated high risk. To elucidate the possible molecular mechanism underlying these neuro-behavioral effects of BPS, we assessed the serotonergic system via changes in mRNA expression of sero-tonin receptors, including the 5-HT1A, 5-HT1B, and 5-HT1D subtypes, the serotonin transporter and monoamine oxidase (MAO). The impaired anxiety and antipredator responses were associated with reduced levels of 5-HT1A subtype and MAO mRNA expression within the brain of adult male offspring. Collectively, the results of this study demonstrate that maternal exposure to environmental concentrations of BPS can interfere with the sero-tonergic signaling pathway in the developing brain, subsequently leading to the onset of a suite of behavioral deficits in adult offspring.