Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
PLoS One. 2012;7(4):e34328. doi: 10.1371/journal.pone.0034328. Epub 2012 Apr 5.
Spontaneous preterm birth (SPB, before 37 gestational weeks) is a major cause of perinatal mortality and morbidity, but its pathogenesis remains unclear. Studies on SPB have been hampered by the limited availability of markers for SPB in predelivery clinical samples that can be easily compared with gestational age-matched normal controls. We hypothesize that SPB involves aberrant placental RNA expression, and that such RNA transcripts can be detected in predelivery maternal plasma samples, which can be compared with gestational age-matched controls.
Using gene expression microarray to profile essentially all human genes, we observed that 426 probe signals were changed by >2.9-fold in the SPB placentas, compared with the spontaneous term birth (STB) placentas. Among the genes represented by those probes, we observed an over-representation of functions in RNA stabilization, extracellular matrix binding, and acute inflammatory response. Using RT-quantitative PCR, we observed differences in the RNA concentrations of certain genes only between the SPB and STB placentas, but not between the STB and term elective cesarean delivery placentas. Notably, 36 RNA transcripts were observed at placental microarray signals higher than a threshold, which indicated the possibility of their detection in maternal plasma. Among them, the IL1RL1 mRNA was tested in plasma samples taken from 37 women. It was detected in 6 of 10 (60%) plasma samples collected during the presentation of preterm labor (≤32.9 weeks) in women eventually giving SPB, but was detected in only 1 of 27 (4%) samples collected during matched gestational weeks from women with no preterm labor (Fisher exact test, p = 0.00056).
We have identified 36 SPB-associated RNA transcripts, which are possibly detectable in maternal plasma. We have illustrated that the IL1RL1 mRNA was more frequently detected in predelivery maternal plasma samples collected from women resulting in SPB than the gestational-age matched controls.
自发性早产（SPB，在 37 孕周之前）是围产儿死亡和发病的主要原因，但发病机制仍不清楚。SPB 的研究受到限制，因为在分娩前的临床样本中，能够与胎龄匹配的正常对照相比的 SPB 标志物的可用性有限。我们假设 SPB 涉及异常的胎盘 RNA 表达，并且这种 RNA 转录本可以在分娩前的母血浆样本中检测到，可以与胎龄匹配的对照进行比较。
使用基因表达微阵列对几乎所有人类基因进行分析，我们观察到，与自发性足月分娩（STB）胎盘相比，SPB 胎盘中有 426 个探针信号的变化超过 2.9 倍。在这些探针所代表的基因中，我们观察到 RNA 稳定、细胞外基质结合和急性炎症反应功能的过度表达。使用 RT-定量 PCR，我们仅观察到 SPB 和 STB 胎盘之间某些基因的 RNA 浓度存在差异，而不是 STB 和择期剖宫产胎盘之间。值得注意的是，在胎盘微阵列信号高于阈值的情况下观察到 36 个 RNA 转录本，这表明它们有可能在母血浆中检测到。其中，IL1RL1 mRNA 在来自 37 名妇女的血浆样本中进行了测试。在最终发生 SPB 的妇女的早产（≤32.9 周）发作期间采集的 10 个（60%）血浆样本中检测到 6 个，但在没有早产的妇女的匹配胎龄采集的 27 个（4%）样本中仅检测到 1 个（Fisher 精确检验，p=0.00056）。
我们已经确定了 36 个与 SPB 相关的 RNA 转录本，这些转录本可能在母血浆中检测到。我们已经说明，在分娩前的母血浆样本中，与胎龄匹配的对照组相比，从导致 SPB 的妇女中更频繁地检测到 IL1RL1 mRNA。
