环境雌激素E2、o,p′-DDT和抗雌激素TAM对斑马鱼(Danio rerio)胚胎的二元联合毒性效应(英文)

Effects of Binary Mixtures of Environment Estrogens E2,o,p'-DDT and Antiestrogen TAM on Zebrafish(Danio rerio) Embryos

为了探究雌激素与抗雌激素类化合物的联合毒性效应,将斑马鱼胚胎暴露于雌激素17β-雌二醇(E2)和o,p′-DDT,抗雌激素它莫昔芬(TAM)以及雌激素(E2、DDT)与抗雌激素(TAM)的二元混合物96h,观察其形态学变化(孵化率、畸形率和孵化时间)以及测定雌激素效应相关基因(VTG1,VTG2和ERα)的转录水平。结果显示,暴露于E2(0.25μg/L),o,p′-DDT(100μg/L)与TAM(10,50,250μg/L)的二元混合物组可致斑马鱼的畸形率上升、孵化率下降、孵化时间延长,混合暴露组与单独暴露组差异显著(P<0.05)。例如当E2浓度为0.25μg/L,TAM浓度为50μg/L,混合暴露组孵化率为57.2%,显著低于单独暴露于E2的82.5%以及单独暴露于TAM的90.4%。在胚胎发育形态学水平上,未观察到二元混合物组繁殖毒性明显减低的现象;在基因转录水平上,TAM对雌激素并不是单纯的拮抗作用,其作用随暴露浓度不同而有所改变。实验表明,抗雌激素TAM与雌激素E2及DDT的混合暴露提高了对斑马鱼的毒害作用。

Zebrafish（Danio rerio）embryos were exposed to 17β-estradiol（E2）,o,p′-DDT and tamoxifen（TAM）to evaluate the combined effects of endocrine disrupting chemicals（EDCs）on animal reproduction.Hatchability,gross abnormalities rate,hatching time and expressions of estrogen-responsive genes of embryos were observed after 96 hours of exposure.Embryos exposed to compounds with E2（0.25μg/L）or TAM（10,50,250μg/L）or binary mixtures of o,p′-DDT（100μg/L）and TAM（10,50,250μg/L）resulted in significant impairments in reproductive performance compared to embryos exposed to one kind of EDC.For example,hatchability of mixture group E2（0.25μg/L）and TAM（50μg/L）was 57.2%,significantly lower than that of embryos exposed to E2alone（82.5%）or TAM alone（90.4%）.TAM cannot neutralize the effects of E2 and o,p′-DDT on embryo morphological development.On gene transcription level,TAM is not entirely antagonistic against estrogen,instead,the property it behaves depends on its concentration.Our observations illustrate that binary mixtures can make a rise to toxicity and reproductive harm to zebrafish.The possibility that the reproduction effects of estrogen can be neutralized by antiestrogen in aquatic organisms should be questioned.