Time- and dose-dependent detoxification and reproductive endocrine disruption induced by tetrabromobisphenol A (TBBPA) in mussel Mytilus galloprovincialis

Abstract

As a typical brominated flame retardant (BFR), tetrabromobisphenol A (TBBPA) has been frequently detected in both biotic and abiotic matrices in marine environment. Our previous study found that genes related to metabolism phase I/II/III as well as steroid metabolism in Mytilus galloprovincialis were significantly altered by TBBPA treatment. However, the time- and dose-dependent response profiles of these genes to TBBPA exposure were rarely reported. In this study, the time- and dose-dependent effects of TBBPA on detoxification and reproductive endocrine disruption in M. galloprovincialis were explored by evaluating the responses of related gene expressions, enzymatic activities and gametogenesis to different concentrations of TBBPA (0.6, 3, 15, 75 and 375 μg/L) for different durations (14, 21 and 28 days). The results showed that the TBBPA accumulation increased linearly with the increases of exposure time and dose. Cytochrome P450 family 3 (CYP3A1-like) cooperated with CYP4Y1 for phase I biotransformation of TBBPA in mussels. The dose-response curves of phase II/III genes (glutathione-S-transferase (GST), P-glycoprotein (ABCB), and multidrug resistance protein (ABCC)) showed similar response profiles to TBBPA exposure. The common induction of phase I/II/III (CYPs, GST, ABCB and ABCC) suggested TBBPA detoxification regulation in mussels probably occurred in a step-wise manner. Concurrently, direct sulfation mediated by sulfotransferases (SULTs) on TBBPA was also the vital metabolic mechanism for TBBPA detoxification, which was supported by the coincidence between up-regulation of SULT1B1 and TBBPA accumulation. The significant promotion of steroid sulfatase (STS) might result from TBBPA-sulfate catalyzed by SULT1B1 due to its chemical similarity to estrone-sulfate. Furthermore, the promotion of gametogenesis was consistent with the induction of STS, suggesting that STS might interrupt steroids hydrolysis process and was responsible for reproductive endocrine disruption in M. galloprovincialis. This study provides a better understanding of the detoxification and endocrine-disrupting mechanisms of TBBPA.