Time- and dose-dependent detoxification and reproductive endocrine disruption induced by tetrabromobisphenol A (TBBPA) in mussel Mytilus galloprovincialis
Time- and dose-dependent detoxification and reproductive endocrine disruption induced by tetrabromobisphenol A (TBBPA) in mussel Mytilus galloprovincialis
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DOI：
10.1016/j.marenvres.2022.105839
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发表时间：
2022-12-05
影响因子：
3.3
通讯作者：
Ji，Chenglong
中科院分区：
文献类型：
--
作者：
Wang，Shuang;Sun，Zuodeng;Ji，Chenglong
四溴双酚A（TBBPA）是一种典型的溴系阻燃剂，在海洋环境中的生物和非生物基质中经常被发现。我们前期的研究发现，TBBPA处理后，贻贝代谢I/II/III期相关基因以及类固醇代谢相关基因发生了显著改变。然而，这些基因的时间和剂量依赖性的反应曲线TBBPA曝光很少报道。本研究探讨了TBBPA对M.结果表明，TBBPA对小鼠胚胎发育的影响主要表现在胚胎发育过程中的基因表达、酶活性和配子发生等方面，TBBPA浓度为0.6、3、15、75和375 μg/L，作用时间为14、21和28 d。结果表明，TBBPA的累积量随暴露时间和剂量的增加而线性增加。细胞色素P450家族3（CYP 3A 1-like）与CYP 4 Y1协同参与贻贝中TBBPA的I相生物转化。II/III期基因（谷胱甘肽-S-转移酶（GST），P-糖蛋白（ABCB），和多药耐药蛋白（ABCC））的剂量-反应曲线显示出类似的响应曲线TBBPA暴露。贻贝中TBBPA的I/II/III期（CYP、GST、ABCB和ABCC）的共同诱导表明TBBPA的解毒调节可能是以逐步的方式发生的。同时，由磺基转移酶（sulfotransferases，SULT）介导的TBBPA的直接硫酸化作用也是TBBPA解毒的重要代谢机制，这一点得到了SULT 1B 1的上调与TBBPA积累之间的一致性的支持。由于SULT 1B 1与雌酮硫酸酯的化学结构相似，其对甾体硫酸酯酶（STS）活性的显著促进作用可能是由其催化的TBBPA硫酸酯引起的。此外，STS对配子发生的促进作用与STS对配子发生的诱导作用一致，表明STS可能干扰了雄激素的水解过程，从而影响了雄激素对生殖内分泌的影响。galloprovincialis。这项研究提供了更好的理解TBBPA的解毒和内分泌干扰机制。
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 inM. galloprovincialiswere 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 withCYP4Y1for 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,ABCBandABCC) 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 ofSULT1B1and 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 ofSTS, suggesting thatSTSmight interrupt steroids hydrolysis process and was responsible for reproductive endocrine disruption inM. galloprovincialis. This study provides a better understanding of the detoxification and endocrine-disrupting mechanisms of TBBPA.