Microarray analysis of uterine gene expression in mouse and human pregnancy

Microarray analysis of uterine gene expression in mouse and human pregnancy
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DOI:
10.1210/me.2003-0007
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发表时间:
2003-08-01
影响因子:
--
通讯作者:
Muglia, LJ
Muglia, LJ
中科院分区:
医学2区
文献类型:
--
作者:
Bethin, KE;Nagai, Y;Muglia, LJ

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改善对早产儿的护理提高了他们的存活率。然而,早产的发生率并没有改变。为了了解早产的过程,我们使用寡核苷酸微阵列来研究怀孕期间小鼠和人类子宫中的基因表达。前列腺素合成酶的诱导被用作妊娠期间重要变化的标志,因为野牡丹素对人类和小鼠的分娩都有很大贡献。我们在妊娠小鼠子宫中发现了504个基因,这些基因在第13.5天至19.0天之间至少发生了2倍的变化。在怀孕的人子宫肌层中,我们发现478个基因在足月或早产中与早产非分娩样本相比至少变化了2倍,77个基因在早产和足月分娩中变化显著。功能组内的基因调控模式比较人类早产和足月分娩是相似的,虽然变化的幅度往往各不相同。令人惊讶的是,在整个怀孕期间发生显著变化的基因在小鼠和人类中几乎没有相同的。这些数据表明,在人类子宫肌层的功能性孕酮撤退可能不是引产的主要机制,可能涉及人类特发性早产和足月分娩的类似机制,并可能为进一步研究确定新的目标。
Improved care of infants born prematurely has increased their survival. However, the incidence of preterm labor has not changed. To understand the processes involved in preterm labor, we used oligonucleotide microarrays to study gene expression in murine and human uterus during pregnancy. The induction of enzymes for prostaglandin synthesis was used as a marker for important changes during pregnancy because prostaglandins strongly contribute to both human and murine labor. We identified 504 genes that changed at least 2-fold between d 13.5 and 19.0 in the gravid mouse uterus. In the pregnant human myometrium, we found 478 genes that changed at least 2-fold in either term or preterm labor compared with preterm nonlabor specimens and 77 genes that significantly varied in both preterm and term labor. Patterns of gene regulation within functional groups comparing human preterm and term labor were similar, although the magnitude of change often varied. Surprisingly, few genes that changed significantly throughout pregnancy were the same in the mouse and human. These data suggest that functional progesterone withdrawal in human myometrium may not be the primary mechanism for labor induction, may implicate similar mechanisms for idiopathic preterm and term labor in humans, and may identify novel targets for further study.