Tetrabromobisphenol S alters the circadian rhythm network in the early life stages of zebrafish

Tetrabromobisphenol S (TBBPS), an emerging brominated flame retardant (BFR) has been widely detected in the environment, and may potentially pose environmental risks. However, data on the occurrence and toxic effects of TBBPS are limited. Circadian rhythms govern multiple behavioral and physiological processes, and their disruption is closely associated with various pathological conditions. Little is known about the potential for TBBPS to perturb circadian rhythm networks or circadian-driven locomotor behavior. In the present study, behavior assays and gene expression analysis based on circadian rhythm pathways were designed to investigate the potential circadian rhythm impairments and subsequent adverse effects caused in 120 h post-fertilization (hpf) zebrafish larvae by TBBPS. The development of embryos was inhibited by TBBPS exposure even at concentrations below the maximal non-lethal concentration (MNLC, 3.47 mg/L). Our results indicated remarkable alterations in the expression of several key circadian rhythm genes due to TBBPS exposure. Compared to control, the expression of per1a, per1b, per3, cry2, and csnk1da was increased, while the expression of clocka, clockb, cry4, cry1ba, arntl1a, and cank1db was decreased. Significant alterations of the circadian rhythm network could be observed in the zebrafish embryos. TBBPS exposure also significantly affected the behavioral responses of larvae. Our findings suggest the circadian rhythm network could be a potential target of TBBPS. Further study is needed to explore whether the transcriptional alterations in circadian rhythm translate into physiological effects.