| 2,2’,4,4’-Tetrabromodiphenyl ether (BDE-47),6-hydroxy-tetrabromodiphenyl ether (6-OH-BDE-47) and 6-methoxy-tetrabromodiphenyl ether (6-MeO-BDE-47) were the most detected isomers of polybrominated diphenyl ether (PBDE), OH-BDEs and MeO-BDEs in aquatic organisms. They were reported to have reproduction toxicity as well as endocrine disrupting effects. However, limitations as followed still exist in the aquatic toxicological field (fish for example):(1) BDE-47 and its derivates which detected in the embryos were inherited by parent-larva exposure way, however, because of adsorption, intaken, bioaccumulation and metabolisms of compounds in exposure solution, the internal concentration and the exposure concentration were distinct. Obviously, it was limited to use the traditional waterborne exposure in studying the actual dose-effect relationship. (2) BDE-47 could affect hypothalamus-pituitary-thyroid (HPT) axis in organisms that the expression of related genes, thyroid function and thyroid hormone concentrations could be altered. However, the thyroid gland toxicity of 6-OH-BDE-47 and 6-MeO-BDE-47 has not been reported. (3) BDE-47 has been confirmed to have endocrine interference effects mediated through multiple receptors, but the researches were mainly based on separated cells of mammals. Due to the different sources, the results were usually contradicted. The research about the derivatives of BDE-47 was rare.BDE-47,6-OH-BDE-47 and 6-MeO-BDE-47 were chosen as the target compounds in this study. Waterborne exposure and nanoinjection method were applied to study the effects on zebrafish at the early developmental stages. The advantages of nanoinjection in studying the internal dose-effects were evaluated by means of chemical analysis. In order to judge whether BDE-47 and its derivates affected the normal function by influencing the HPT axis biological signaling pathways or not, q-RT-PCR technique was used to detect the mRNA expression of HPT axis-related genes in zebrafish embryos/larvae after exposed to BDE-47, 6-MeO-BDE-47 and 6-OH-BDE-47. In this study, q-RT-PCR was also used to detect the mRNA expression of genes associated to aryl hydrocarbon receptor (AhR), estrogen receptor (ER), androgen receptor (AR), thyroid hormone receptor (TR), peroxisome proliferator activated receptor (PPAR), pregnane X receptor (PxR), glucocorticoid receptor (GR) and mineralocorticoid receptor (MR).The results were as follows:The developmental effects of BDE-47 and its derivates in zebrafish embryo by different exposure way showed that 6-OH-BDE-47 was the most potent compound of all and it could result in developmental delay and even acute lethal effects; Severe edema, spinal curvature of zebrafish embryo/larva were observed in the high concentrations of 6-MeO-BDE-47, and shorter body length was appeared subsequently; Minimal apparent effects of BDE-47 was found in this study. The overall performance order of bioaccumulation was 6-MeO-BDE-47> BDE-47> 6-OH-BDE-47.6-MeO-BDE-47 can be transformed into 6-OH-BDE-47 which was more toxic than 6-MeO-BDE-47 in organisms. Nanoinjection was confirmed an excellent exposure way to determine the dose-effect relationship of lipophilic PBDEs and their derivates.Effects of target compounds on HPT axis showed that the influence of compounds in HPT axis at low concentrations could be a good warning of their developmental effects.6-OH-BDE-47 and 6-MeO-BDE-47 could affect the HPT axis in opposite, but the interference capability of BDE-47 was the least.In this study, the zebrafish embryo/larval screening model was confirmed to be an excellent model in detecting the activity of 8 receptors. The endocrine disrupting effects were different among the compounds. It showed that the endocrine disruping effects of 6-OH-BDE-47 were potentially mediated by AhR, ER and MR, while the effects of 6-MeO-BDE-47 might AhR, ER, TR, AR and GR mediated and the effects of BDE-47 were potentially mediated by AhR, ER and GR. |
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