Regulation and Function of Deiodinases During Decidualization in Female Mice
Regulation and Function of Deiodinases During Decidualization in Female Mice
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雌性小鼠蜕膜化过程中脱碘酶的调控和功能
DOI：
10.1210/en.2014-1015
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发表时间：
2014-07-01
期刊：
影响因子：
4.8
通讯作者：
Yang, Zeng-Ming
中科院分区：
文献类型：
--
作者：
Deng, Wen-Bo;Liang, Xiao-Huan;Yang, Zeng-Ming
人类妊娠期间的甲状腺功能障碍与严重的妊娠结局密切相关。然而，妊娠早期甲状腺激素的调节和功能尚不清楚。我们发现 II 型脱碘酶（一种将 T-4 转化为活化 T-3 的酶）在怀孕第 3 天和第 4 天的小鼠子宫中高度表达。一旦胚胎植入接受子宫，III型脱碘酶（Dio3）（一种主要用于灭活T-3的父系印记基因）就会在基质细胞中显着诱导，并伴随着delta-like 1同源物-Dio3印记簇中基因间差异CpG甲基化区域的DNA高甲基化。子宫游离T-3的浓度实际上在胚胎植入后降低。 T-3 在体内和体外均诱导 Dio3 表达，表明存在正反馈循环。 T-3 添加或 Dio3 敲低会损害蜕膜化。这些结果表明 Dio3 介导的局部 T-3 减少对于妊娠早期基质细胞的蜕膜化至关重要。此外，我们发现孕酮在体内和体外都通过其同源受体调节 Dio3 的表达。此外，cAMP 通过蛋白激酶 A-cAMP 反应元件结合蛋白途径调节 Dio3 转录。蛋白激酶 A 通路的抑制导致 Dio3 表达减少和蜕膜化受损。 Dio3 相反链 (Dio3os) 以与 Dio3 相似的模式表达，从 Dio3 的相反链转录，并在蜕膜化过程中微调 Dio3 的表达。我们的数据表明 Dio3 在蜕膜化过程中强烈表达并受到严格控制。
Thyroid dysfunction during human pregnancy is closely related to serious pregnancy outcome. However, the regulation and function of thyroid hormones during early pregnancy are largely unknown. We found that type II deiodinase, an enzyme converting T-4 to activated T-3, is highly expressed in the mouse uterus on days 3 and 4 of pregnancy. Once the embryo implants into the receptive uterus, type III deiodinase (Dio3), a mainly paternally imprinted gene for inactivating T-3, is significantly induced in the stromal cells and accompanied by DNA hypermethylation of intergenic differentially CpG methylation regions in the delta-like 1 homolog-Dio3 imprinting cluster. The concentration of uterine free T-3 is actually decreased after embryo implantation. T-3 induces Dio3 expression both in vivo and in vitro, suggesting a positive feedback loop. T-3 addition or Dio3 knockdown compromises decidualization. These results indicate that the Dio3-mediated local T-3 decrease is critical for decidualization of stromal cells during early pregnancy. Furthermore, we found that progesterone regulates Dio3 expression through its cognate receptor both in vivo and in vitro. Additionally, cAMP regulates Dio3 transcription through the protein kinase A-cAMP response element-binding protein pathway. The inhibition of the protein kinase A pathway results in decreased Dio3 expression and impaired decidualization. Dio3 opposite strand (Dio3os) expressed in a similar pattern to Dio3, is transcribed from the opposite strand of Dio3 and fine-tunes Dio3 expression during decidualization. Our data indicate that Dio3 is strongly expressed and tightly controlled during decidualization.