...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Endocrinology >Hypermethylation of homeobox A10 by in utero diethylstilbestrol exposure: an epigenetic mechanism for altered developmental programming.
【24h】

Hypermethylation of homeobox A10 by in utero diethylstilbestrol exposure: an epigenetic mechanism for altered developmental programming.

机译：子宫二乙基雌甾醇暴露引起的同源盒A10的超甲基化：改变发育程序的表观遗传机制。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Diethylstilbestrol (DES) is a nonsteroidal estrogen that induces developmental anomalies of the female reproductive tract. The homeobox gene HOXA10 controls uterine organogenesis, and its expression is altered after in utero DES exposure. We hypothesized that an epigenetic mechanism underlies DES-mediated alterations in HOXA10 expression. We analyzed the expression pattern and methylation profile of HOXA10 after DES exposure. Expression of HOXA10 is increased in human endometrial cells after DES exposure, whereas Hoxa10 expression is repressed and shifted caudally from its normal location in mice exposed in utero. Cytosine guanine dinucleotide methylation frequency in the Hoxa10 intron was higher in DES-exposed offspring compared with controls (P = 0.017). The methylation level of Hoxa10 was also higher in the caudal portion of the uterus after DES exposure at the promoter and intron (P < 0.01). These changes were accompanied by increased expression of DNA methyltransferases 1 and 3b. No changes in methylation were observed after in vitro or adult DES exposure. DES has a dual mechanism of action as an endocrine disruptor; DES functions as a classical estrogen and directly stimulates HOXA10 expression with short-term exposure, however, in utero exposure results in hypermethylation of the HOXA10 gene and long-term altered HOXA10 expression. We identify hypermethylation as a novel mechanism of DES-induced altered developmental programming.
机译：己烯雌酚（DES）是一种非甾体雌激素，可诱发女性生殖道发育异常。同源盒基因HOXA10控制子宫器官的发生，在子宫DES暴露后其表达发生改变。我们假设表观遗传机制是HOXA10表达中DES介导的变化的基础。我们分析了DES暴露后HOXA10的表达模式和甲基化谱。在DES暴露后，人类子宫内膜细胞中HOXA10的表达增加，而在子宫内暴露的小鼠中，Hoxa10的表达受到抑制，并从其正常位置向尾状移动。与对照相比，在DES暴露的后代中，Hoxa10内含子中的胞嘧啶鸟嘌呤二核苷酸甲基化频率更高（P = 0.017）。在启动子和内含子暴露于DES后，子宫的尾部Hoxa10的甲基化水平也更高（P <0.01）。这些变化伴随着DNA甲基转移酶1和3b表达的增加。在体外或成人DES暴露后，未观察到甲基化的变化。 DES作为内分泌干扰物具有双重作用机制。 DES具有经典的雌激素功能，可通过短期暴露直接刺激HOXA10表达，但是，在子宫内暴露会导致HOXA10基因超甲基化和长期改变HOXA10表达。我们确定超甲基化为DES诱导改变发育规划的一种新型机制。

著录项

相似文献

  • 外文文献
  • 中文文献
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号