Maternal High Estradiol Exposure is Associated with Elevated Thyroxine and Pax8 in Mouse Offspring.
Maternal High Estradiol Exposure is Associated with Elevated Thyroxine and Pax8 in Mouse Offspring.
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母体高雌二醇暴露与小鼠后代甲状腺素和 Pax8 升高有关
DOI：
10.1038/srep36805
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发表时间：
2016-11-09
影响因子：
4.6
通讯作者：
Huang HF
中科院分区：
文献类型：
--
作者：
Lv PP;Tian S;Feng C;Li JY;Yu DQ;Jin L;Shen Y;Yu TT;Meng Y;Ding GL;Jin M;Chen XJ;Sheng JZ;Zhang D;Huang HF
我们以前的研究表明，母亲高雌二醇（E2）环境增加了后代甲状腺功能障碍的风险。然而，所涉及的机制仍未得到探讨。为评价高雌二醇暴露对子代甲状腺功能的影响并探讨其可能机制，建立了高雌二醇早孕小鼠模型，并对其子代甲状腺激素进行了检测。在子代甲状腺中，分析Tg、Nis、Tpo、Pax8和Titf1的表达，以及Pax8和甲基化相关基因的CpG岛甲基化状态。结果发现，高雌二醇组仔鼠甲状腺素（T_4）和游离甲状腺素（FT_4）水平明显升高，尤以雌鼠为甚。在高E2组的3周龄和8周龄的后代中，Pax8在甲状腺中显著上调，伴随着启动子区域的异常CpG岛甲基化状态。高E2组甲状腺Dnmt 3a和Mbd 1表达明显下调。此外，女性甲状腺功能紊乱比男性严重，提示其影响与性别有关。总之，我们的研究表明，母亲高E2暴露通过Pax8的失调和异常DNA甲基化干扰后代的甲状腺功能。
Our previous studies have shown that maternal high estradiol (E2) environment increased the risk of thyroid dysfunction in offspring. However, the mechanism involved remains unexplored. To evaluate the thyroid function of offspring after high E2 exposure and to explore the underlying mechanism, we established a high E2 mouse model of early pregnancy, and detected thyroid hormones of their offspring. In thyroids of offspring, the expressions of Tg, Nis, Tpo, Pax8, and Titf1 and CpG island methylation status of Pax8 and genes involved in methylation were analyzed. We found that thyroxine (T4) and FT4 levels of offspring were obviously increased in the high-E2 group, especially in females. In both 3- and 8-week-old offspring of the high-E2 group, Pax8 was significantly up-regulated in thyroid glands, accompanied by the abnormal CpG island methylation status in the promoter region. Furthermore, Dnmt3a and Mbd1 were obviously down-regulated in thyroids of the high E2 group. Besides, the disturbance of thyroid function in females was more severe than that in males, implying that the effects were related to gender. In summary, our study indicated that maternal high E2 exposure disturbed the thyroid function of offspring through the dysregulation and abnormal DNA methylation of Pax8.
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影响因子：
2.7
作者：
Banu, SK;Govindarajulu, P;Aruldhas, MM
通讯作者：
Aruldhas, MM
影响因子：
64.8
作者：
Ng, Sheau-Fang;Lin, Ruby C. Y.;Morris, Margaret J.
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Morris, Margaret J.
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影响因子：
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作者：
OSMOND, C;BARKER, DJP;SIMMONDS, SJ
通讯作者：
SIMMONDS, SJ
影响因子：
64.5
作者：
Okano, M;Bell, DW;Li, E
通讯作者：
Li, E