环境雌激素与抗雌激素对斑马鱼胚胎的复合效应研究
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摘要
目前有关环境内分泌干扰物(endocrine disrupting chemicals, EDCs)的复合效应研究主要集中于同类EDCs的联合效应,不同种类EDCs复合效应研究亟需加强。将经典模式生物斑马鱼胚胎暴露于雌激素17β-雌二醇(E2)、o,p'-DDT,抗雌激素它莫昔芬(TAM)、氟维司群及其二元混合物中。观察胚胎孵化率、孵化时间和总畸形率,并用荧光实时定量PCR检测VTG1、VTG2、ERα等雌激素效应相关基因mRNA转录水平。对四种EDCs间复合效应进行分析、评价,以期为全面了解雌激素类与抗雌激素类的复合效应提供一定科学依据。主要研究结果如下:
(1)单一EDCs作用对斑马鱼胚胎发育形态学有不同程度的影响;VTG基因被雌激素诱导表达量增加,ERα基因表达被抗雌激素氟维司群所抑制。单独存在的TAM表现出弱雌激素效应。
(2)传统观点认为,环境雌激素效应可能会被抗雌激素等物质所平衡,但在胚胎发育形态学水平上,雌激素与抗雌激素混合物并没出现因为雌激素与抗雌激素相互作用而使繁殖毒性减轻的情况。另外,和胚胎孵化时间相比,胚胎孵化率、总畸形率更好地体现出联合毒性效应。
(3)在基因转录水平上,雌激素与抗雌激素二元混合物中总体上二者表现出了相互拮抗的效应,即抗雌激素的存在减轻了雌激素效应。不过o,p'-DDT与TAM共暴露组中,高浓度的TAM显示了弱雌激素的作用。
上述结论表明抗雌激素并非简单地抑制环境雌激素的生态毒性效应,在进行生态风险评价时需全面评估雌激素与抗雌激素的复合效应。
At present the most study of research in endocrine disrupting chemicals (EDCs) are study of compound effect of the same kind of EDCs. Study of different kinds need to be strengthen. In this study, after exposure to the typical estrogen 17β-estradiol(E2), o,p'-DDT and antiestrogen tamoxifen(TAM), fulvestrant, morphology levels of toxicological endpoints of zebrafish (Danio rerio) embryos such as hatching rate, hatching time and gross abnormalities rate were observed. Then real-time quantitative PCR was used to investigate the changes in transcription of mRNA of estrogen-responsive gene such as VTG1, VTG2 and ERα. The combined effects between the four EDCs were analyzed and evaluated to provide a scientific basis for comprehensive understanding the combination effects between estrogen and antiestrogen. The major findings are as follows:
(1) Single EDCs impacted morphology of zebrafish embryos. Expression of VTG gene was increased because of estrogen inducing. Expression of ERαgene was inhibited by fulvestrant. TAM showed a weak estrogenic effect.
(2) At morphological level in embryonic development, reproductive toxicity in mixtures did not decrease because of interactions between antiestrogen and estrogen,which was different from the traditional view. In addition, compared to the gross abnormalities rate and the hatching rate, the hatching time of embryos did not reflect well the compound effect.
(3) At the level of gene transcription, estrogen and antiestrogen in the binary mixtures generally showed a antagonistic effect, which meant the antiestrogen reduced the effects of estrogen. But in the binary mixtures of o,p'-DDT and TAM, high concentrations of TAM showed a weak estrogen effects and did not showed obvious antagonistic effect to o,p'-DDT.
It could be indicated from the findings that antiestrogen did not simply inhibit the ecotoxicological effects of estrogen. So we should evaluate the combination effects of estrogens and antiestrogens comprehensively when conduct ecological risk assessment.
(1)单一EDCs作用对斑马鱼胚胎发育形态学有不同程度的影响;VTG基因被雌激素诱导表达量增加,ERα基因表达被抗雌激素氟维司群所抑制。单独存在的TAM表现出弱雌激素效应。
(2)传统观点认为,环境雌激素效应可能会被抗雌激素等物质所平衡,但在胚胎发育形态学水平上,雌激素与抗雌激素混合物并没出现因为雌激素与抗雌激素相互作用而使繁殖毒性减轻的情况。另外,和胚胎孵化时间相比,胚胎孵化率、总畸形率更好地体现出联合毒性效应。
(3)在基因转录水平上,雌激素与抗雌激素二元混合物中总体上二者表现出了相互拮抗的效应,即抗雌激素的存在减轻了雌激素效应。不过o,p'-DDT与TAM共暴露组中,高浓度的TAM显示了弱雌激素的作用。
上述结论表明抗雌激素并非简单地抑制环境雌激素的生态毒性效应,在进行生态风险评价时需全面评估雌激素与抗雌激素的复合效应。
At present the most study of research in endocrine disrupting chemicals (EDCs) are study of compound effect of the same kind of EDCs. Study of different kinds need to be strengthen. In this study, after exposure to the typical estrogen 17β-estradiol(E2), o,p'-DDT and antiestrogen tamoxifen(TAM), fulvestrant, morphology levels of toxicological endpoints of zebrafish (Danio rerio) embryos such as hatching rate, hatching time and gross abnormalities rate were observed. Then real-time quantitative PCR was used to investigate the changes in transcription of mRNA of estrogen-responsive gene such as VTG1, VTG2 and ERα. The combined effects between the four EDCs were analyzed and evaluated to provide a scientific basis for comprehensive understanding the combination effects between estrogen and antiestrogen. The major findings are as follows:
(1) Single EDCs impacted morphology of zebrafish embryos. Expression of VTG gene was increased because of estrogen inducing. Expression of ERαgene was inhibited by fulvestrant. TAM showed a weak estrogenic effect.
(2) At morphological level in embryonic development, reproductive toxicity in mixtures did not decrease because of interactions between antiestrogen and estrogen,which was different from the traditional view. In addition, compared to the gross abnormalities rate and the hatching rate, the hatching time of embryos did not reflect well the compound effect.
(3) At the level of gene transcription, estrogen and antiestrogen in the binary mixtures generally showed a antagonistic effect, which meant the antiestrogen reduced the effects of estrogen. But in the binary mixtures of o,p'-DDT and TAM, high concentrations of TAM showed a weak estrogen effects and did not showed obvious antagonistic effect to o,p'-DDT.
It could be indicated from the findings that antiestrogen did not simply inhibit the ecotoxicological effects of estrogen. So we should evaluate the combination effects of estrogens and antiestrogens comprehensively when conduct ecological risk assessment.
引文
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