The constitutively active Ah receptor (CA-AhR) mouse as a model for dioxin exposure - Effects in reproductive organs
The constitutively active Ah receptor (CA-AhR) mouse as a model for dioxin exposure - Effects in reproductive organs
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DOI：
10.1016/j.chemosphere.2011.09.015
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发表时间：
2011-12-01
期刊：
影响因子：
8.8
通讯作者：
Hanberg, Annika
中科院分区：
文献类型：
--
作者：
Brunnberg, Sara;Andersson, Patrik;Hanberg, Annika
二恶英/芳烃受体 (AhR) 介导二恶英的大部分毒性作用。在子宫内/哺乳期接触 2,3,7,8-四氯二苯并-对二恶英 (TCDD) 会损害胎儿/新生儿的发育，而正在发育的男性生殖道是最敏感的组织之一。在雌激素存在的情况下，TCDD 在啮齿动物乳腺和子宫以及人类乳腺癌细胞系中引起抗雌激素反应。此外，最近有人提出，在缺乏雌激素的情况下，TCDD/AhR 也具有类似雌激素的作用。表达组成型活性 AhR (CA-AhR) 的转基因小鼠被开发为模拟持续暴露于 AhR 激动剂的情况的模型。 CA-AhR 小鼠的雄性和雌性生殖组织的特征在于二恶英暴露后常见的一些影响。性成熟的 CA-AhR 雌性小鼠显示子宫重量减少，而未成熟 CA-AhR 小鼠的子宫营养测定结果导致子宫重量增加。在未成熟小鼠中，TCDD 暴露和 CA-AhR 均增加了雌激素受体靶基因组织蛋白酶 D 的表达。当与 17 β-雌二醇共同治疗时，TCDD 暴露或 CA-AhR 小鼠的组织蛋白酶 D 水平均未增加。在性成熟的雄性CA-AhR小鼠中，睾丸和腹侧前列腺的重量下降，附睾精子储备也减少。本研究的结果与之前对接触二恶英的啮齿动物的研究一致，即激活的 AhR（此处为 CA-AhR）在雌激素存在的情况下会产生抗雌激素作用，但在没有雌激素的情况下会产生雌激素作用。这些结果表明，CA-AhR 小鼠模型是研究早期发育过程中 AhR 持续低活性的有用工具，类似于人类暴露情况。 (C) 2011 Elsevier Ltd. 保留所有权利。
The dioxin/aryl hydrocarbon receptor (AhR) mediates most toxic effects of dioxins. In utero/lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) impairs fetal/neonatal development and the developing male reproductive tract are among the most sensitive tissues. TCDD causes antiestrogenic responses in rodent mammary gland and uterus and in human breast cancer cell lines in the presence of estrogen. Also, more recently an estrogen-like effect of TCDD/AhR has been suggested in the absence of estrogen. A transgenic mouse expressing a constitutively active AhR (CA-AhR) was developed as a model mimicking a situation of constant exposure to AhR agonists. Male and female reproductive tissues of CA-AhR mice were characterized for some of the effects commonly seen after dioxin exposure. Sexually mature CA-AhR female mice showed decreased uterus weight, while an uterotrophic assay in immature CA-AhR mice resulted in increased uterus weight. In immature mice, both TCDD-exposure and CA-AhR increased the expression of the estrogen receptor target gene Cathepsin D. When co-treated with 17 beta-estradiol no increase in Cathepsin D levels occurred in either TCDD-exposed or CA-AhR mice. In sexually mature male CA-AhR mice the weights of testis and ventral prostate were decreased and the epididymal sperm reserve was reduced. The results of the present study are in accordance with previous studies on dioxin-exposed rodents in that an activated AhR (here CA-AhR) leads to antiestrogenic effects in the presence of estrogen, but to estrogenic effects in the absence of estrogen. These results suggest the CA-AhR mouse model as a useful tool for studies of continuous low activity of the AhR from early development, resembling the human exposure situation. (C) 2011 Elsevier Ltd. All rights reserved.