Labor-associated gene expression in the human uterine fundus, lower segment, and cervix.
Labor-associated gene expression in the human uterine fundus, lower segment, and cervix.
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DOI：
10.1371/journal.pmed.0030169
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发表时间：
2006-06
期刊：
影响因子：
15.8
通讯作者：
Thornton S
中科院分区：
文献类型：
--
作者：
Bukowski R;Hankins GD;Saade GR;Anderson GD;Thornton S
早产、进展迟缓和产后出血是产妇和新生儿死亡或发病的常见原因。所有这些都是由于控制分娩的复杂机制的缺陷造成的，这些机制协调了子宫底、子宫下段和宫颈的变化。我们的目的是评估劳动相关的基因表达谱在这些功能不同的领域的人类子宫通过使用微阵列。在分娩开始前（n = 6）或分娩活跃期（n = 7）从足月（平均值± SD = 39.1 ± 0.5 wk）患者中采集子宫底、子宫下段和宫颈样本。使用微阵列（Human Genome U95 A; Affyssin）评估12，626个基因的表达，并在分娩和非分娩样品之间进行比较。具有最大的劳动相关变化和最低的表达变异性的基因可能是分娩的基础，因此基因表达相应地排名。从500个基因的最高排名，我们确定了基因相似的表达谱使用两个独立的聚类技术。两种技术的机会分组概率小于0.01的基因组分别占眼底、下段和子宫颈中500个基因的71.2%、81.8%和79.8%。我们分别在胃底、下段和子宫颈中发现了14、14和12组基因。这使得共调控和共表达基因的网络被发现。同一簇中的许多基因具有相似的功能，或者具有与分娩过程相关的功能。 我们的研究结果提供了许多既定的分娩过程的支持，也描述了新的劳动力基因以前没有与这个过程。阐明这些机制可能是控制分娩的基础，是发展有效治疗主要产科问题（包括早产）及其对母亲和后代健康的长期影响的重要先决条件。分娩，或劳动，虽然是生活中的基本事件，实际上是一个复杂的过程，涉及子宫（子宫）的三个部分共同努力，以排出婴儿。这一过程中一个特别重要的部分是劳动是如何开始的，但人们对此知之甚少。一旦分娩开始，子宫内发生的实际变化是众所周知的，包括子宫壁肌肉（子宫肌层）的收缩和子宫颈（子宫颈）的扩张。这些变化的一些触发因素也是已知的：例如，在非灵长类动物中，雌激素和孕酮的血液水平发生变化，胎儿周围的膜发生变化。先前的研究表明，这些影响可能反过来由许多基因的变化引发，但具体是哪些基因尚不清楚。更多地了解哪些基因在分娩的各个阶段是重要的，可能有助于设计针对分娩中出现的各种问题（如分娩开始失败，或者早产）的治疗方法。我们对触发或需要以协调的方式开始和继续劳动的基因知之甚少。一种被称为DNA微阵列的技术允许研究人员从身体的任何部位提取样本，并使用它来观察数千个基因的活性，所有这些基因都在同一时间。通过分析这些结果，有可能提示在特定过程中可能重要的单个基因或基因组。作者在分娩前从6名妇女的子宫顶部、下部和宫颈取样，7名妇女从分娩开始时取样。所有女性都因医学原因或出于选择而进行剖宫产。然后，在每位女性的每个样本中，他们观察了12，626个已知基因，以了解它们的活性（科学家称这些活性基因为“表达”）。他们发现，基因表达的变化在子宫的三个部分并不相同。在表达变化最大的500个基因中，有28个是子宫上部和下部共有的，这一小群基因可能在子宫上部和下部的分娩中都很重要。作者还将500个基因分为相关组，他们认为这些关系可能在控制分娩方式方面很重要。识别参与分娩的新基因或基因组对于理解分娩如何发生很重要。这项研究的一个局限性是被研究的妇女人数少，这是可以理解的，因为很难获得这样的样本，以及被研究的妇女之间的差异。这类研究的另一个困难是，用于分析表达模式的方法可能会影响结果。然而，按照这类研究的惯例，所有的结果都被放在一个公共数据库中，这样任何人都可以查看它们，如果他们愿意，还可以做进一步的分析。在一篇受委托评论这篇论文的相关文章中，该论文的原始评论者之一罗伯托·罗梅罗（Roberto Romero）就是这样做的。他发现，他的分析结果与作者的分析结果存在差异。他接着讨论了使用这些技术来看待复杂问题有多难的问题，比如劳动是如何开始的。显然，在弄清楚所有这些结果的真正含义之前，还需要做更多的工作。尽管如此，这些研究有可能帮助更多地了解劳动背后的基础科学。 请通过http://dx.doi.org/10.1371/journal.pmed.0030169上的本摘要在线版本访问这些网站。 · Medline Plus有一个关于分娩的链接页面Radek Bukowski及其同事使用微阵列来评估子宫中与分娩相关的基因表达谱，并发现共调节和共表达基因的网络。
Preterm labor, failure to progress, and postpartum hemorrhage are the common causes of maternal and neonatal mortality or morbidity. All result from defects in the complex mechanisms controlling labor, which coordinate changes in the uterine fundus, lower segment, and cervix. We aimed to assess labor-associated gene expression profiles in these functionally distinct areas of the human uterus by using microarrays. Samples of uterine fundus, lower segment, and cervix were obtained from patients at term (mean ± SD = 39.1 ± 0.5 wk) prior to the onset of labor ( n = 6), or in active phase of labor with spontaneous onset ( n = 7). Expression of 12,626 genes was evaluated using microarrays (Human Genome U95A; Affymetrix) and compared between labor and non-labor samples. Genes with the largest labor-associated change and the lowest variability in expression are likely to be fundamental for parturition, so gene expression was ranked accordingly. From 500 genes with the highest rank we identified genes with similar expression profiles using two independent clustering techniques. Sets of genes with a probability of chance grouping by both techniques less than 0.01 represented 71.2%, 81.8%, and 79.8% of the 500 genes in the fundus, lower segment, and cervix, respectively. We identified 14, 14, and 12 those sets of genes in the fundus, lower segment, and cervix, respectively. This enabled networks of co-regulated and co-expressed genes to be discovered. Many genes within the same cluster shared similar functions or had functions pertinent to the process of labor. Our results provide support for many of the established processes of parturition and also describe novel-to-labor genes not previously associated with this process. The elucidation of these mechanisms likely to be fundamental for controlling labor is an important prerequisite to the development of effective treatments for major obstetric problems—including prematurity, with its long-term consequences to the health of mother and offspring. Childbirth, or labor, although a basic event in life, is actually a complex process that involves three parts of the uterus (womb) working together to expel the baby. One particularly important part of the process, which is poorly understood, is how labor begins. The actual changes that occur in the uterus once labor has begun are well known, and include contractions in the muscle of the uterus wall (the myometrium) and dilation of the cervix (the neck of the womb). Some of the triggers for these changes are also known: for example, in non-primate animals changes in the blood levels of the hormones estrogen and progesterone and changes in the membranes that surround the fetus. Previous studies have suggested that these effects are likely, in turn, to be triggered by changes in many genes, but exactly which ones is not clear. Learning more about which genes are important in the various stages of labor may help to design treatments for the various problems that occur in labor (such as failure of labor to begin, or, alternatively, preterm labor). Little is known about the genes that trigger, or are necessary for, labor to start and to continue in a coordinated fashion. A technology known as DNA microarrays allows researchers to take a sample from any part of the body and use it to look at how active many thousands of genes are, all at the same time. By analyzing these results, it is possible to suggest either single genes or groups of genes that may be important in a particular process. The authors took samples from the uterus top, lower part, and cervix of six women before their labor started, and seven from those whose labor had started. All women were having cesarean sections either for medically indicated reasons, or for choice. Then, in each of the samples in each woman, they looked at 12,626 known genes to see how active they were (scientists call these active genes “expressed”). They found that the changes in gene expression were not, generally, the same across the three parts of the uterus. Of the 500 genes with the largest change in expression, 28 were common to both the upper and lower parts of the uterus, and this small group of genes may be important in labor in both the upper and lower parts of the uterus. The authors also classified the 500 genes into related groups, and they believe that these relationships may be important in controlling how labor happens. Identifying new genes or groups of genes involved in labor is important for understanding how labor occurs. One limitation of this study is the small number of women who were studied—which is understandable, given the difficulty of obtaining such samples—and the differences between the women studied. Another difficulty with such studies is that the methods used to analyze the expression patterns can affect the results. However, as is the custom with these types of studies, all the results were placed in a public database so anyone can look at them and, if they wish, do further analyses. In a related Perspective article that was commissioned to comment on this paper, Roberto Romero, one of the original reviewers of the paper, has done just that. He finds that there were differences in the results of his analyses and those of the authors'. He goes on to discuss the question of how hard it is to use these techniques to look at complex problems, such as how labor starts. Clearly, much more work needs to be done before it is clear what all these results really mean. Nonetheless, these studies have the potential to help to understand more about the basic science behind labor. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030169. • Medline Plus has a page of links on childbirth Radek Bukowski and colleagues used microarrays to assess labor-associated gene expression profiles in the uterus and discover networks of co-regulated and co-expressed genes.
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