In utero diethylstilbestrol (DES) exposure alters Hox gene expression in the developing mullerian system
In utero diethylstilbestrol (DES) exposure alters Hox gene expression in the developing mullerian system
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DOI：
10.1096/fasebj.14.9.1101
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发表时间：
2000-06-01
期刊：
影响因子：
4.8
通讯作者：
Taylor, HS
中科院分区：
文献类型：
--
作者：
Block, K;Kardana, A;Taylor, HS
己烯雌酚（DES）在1971年被广泛用于治疗孕妇，其雌性后代在子宫内暴露于DES的生殖道具有解剖异常的特征，本研究表明，在子宫内给药的小鼠产生了一些参与生殖道模式的Hox基因的表达模式的变化。DES产生Hox基因表达的后向移位和生殖道的同质前向转化。在人子宫或宫颈细胞培养中，DES分别诱导HOXA9或HOXA10基因的表达水平约为雌二醇诱导的两倍，DES诱导的表达不受环己胺的抑制，雌激素是一种新型形态因子，其直接调节Hox后基因的表达模式，类似于视黄酸调节Hox前基因的方式。HOX基因表达的改变是DES影响生殖道发育的分子机制。Hox基因表达的变化是子宫内药物使用影响的潜在标志，可能仅在发育后期才变得明显。-Block， K., Kardana， A., Igarashi， P., Taylor， H. S.。子宫内暴露于己烯雌酚（DES）会改变发育中的苗勒管系统中Hox基因的表达。
Diethylstilbestrol (DES) was widely used to treat pregnant women through 1971, The reproductive tracts of their female offspring exposed to DES in utero are characterized by anatomic abnormalities, Here we show that DES administered to mice in utero produces changes in the expression pattern of several Hox genes that are involved in patterning of the reproductive tract. DES produces posterior shifts in Hox gene expression and homeotic anterior transformations of the reproductive tract. In human uterine or cervical cell cultures, DES induces HOXA9 or HOXA10 gene expression, respectively, to levels approximately twofold that induced by estradiol, The DES-induced expression is not inhibited by cyclohexamide, Estrogens are novel morphogens that directly regulate the expression pattern of posterior Hox genes in a manner analogous to retinoic acid regulation of anterior Hox genes. Alterations in HOX gene expression are a molecular mechanism by which DES affects reproductive tract development. Changes in Hox gene expression are a potential marker for the effects of in utero drug use that may become apparent only at late stages of development.-Block, K., Kardana, A., Igarashi, P., Taylor, H. S. In utero diethylstilbestrol (DES) exposure alters Hox gene expression in the developing mullerian system.