Comparison of maternal and umbilical cord blood HIF-1α and nitric oxide levels in early and late onset preeclamptic pregnancies

Abstract

Objective: Despite the absence of a complete physiologic–pathologic understanding, common accepted theory for development of preeclampsia is incomplete trophoblastic invasion leading to failed uterine and spiral arteriolar remodeling, causing maternal vascular endothelial dysfunction by secreted molecules in response to decreased placental perfusion, placental hypoxia, and ischemia. Placental angiogenesis is especially ineffective in early onset preeclampsia and fetal morbidity/mortality rates are higher because of further decreased blood flow. In this study, we aim to compare the maternal and umbilical cord blood levels of hypoxia-inducible transcription factor-1α (HIF-1α), which is believed to regulate hypoxia-related transcriptional responses, to play role in activating genes for initial phases of placental development and angiogenesis and a physiologic vasodilator molecule nitric oxide (NO) in normal, early and late onset preeclamptic pregnant women.

Methods: Pregnant women who were diagnosed with preeclampsia (early onset ≤34 weeks; late onset >34 weeks) and delivered in our clinic were enrolled for this prospective case-controlled study. Pregnant women without preeclampsia were recruited as control group. HIF-1α and NO levels in maternal and umbilical cord blood measured and compared among groups.

Findings: A total of 46 cases were enrolled for this study, including 25 preeclamptic (13 in the early onset group and 12 in the late onset group) and 21 normal pregnant women in the control group. Comparison of preeclampsia group to controls revealed higher maternal blood HIF-1α levels in the control group, however higher umbilical cord NO levels in the preeclampsia group (p < 0.05 and p < 0.001, respectively). In a second analysis, when compared to control group, both early and late onset preeclampsia subgroups were found to have higher umbilical cord blood NO levels (p < 0.001).

Results: In this study, we observed lower maternal blood HIF-1α levels and higher umbilical cord NO levels in preeclampsia group than controls. These findings suggest that umbilical cord blood NO levels in pregnant women with preeclampsia increase in response to hypoxia. However, lower HIF-1α levels in preeclampsia group can be due to our limited number of cases and we think that there is a need for further studies with larger sample size.

Chinese abstract

目的：尽管对子痫前期的病理—生理过程理解尚不完整，但目前普遍接受的理论认为，子痫前期的发生是由于滋养细胞浸润不完全，从而导致子宫和螺旋动脉重塑失败，母体血管内皮功能紊乱，进而释放分子降低了胎盘灌注量、胎盘低氧供状态、以及局部缺血发生。胎盘血管再生失败在子痫前期尤为突出，胎儿患病率/死亡率也升高了，这是因为远期血液流速降低。在这项研究中，我们旨在比较低氧诱导因子1α（HIF-1α），这是调节低氧相关的转录反应的重要因子，它在激活胎盘和血管形成早期阶段的相关基因方面也发挥重要作用，以及生理性血管舒张因子一氧化氮（NO）在正常、早期及晚期子痫前期妊娠女性中母体和脐带血中的水平。

方法：本前瞻性病例-对照研究纳入了在我院门诊就诊并诊断为子痫前期的妊娠女性（早发性为≤34周；晚发性为＞34周）。妊娠未合并有子痫前期的女性也纳入到实验中作为对照组。比较两组中母体和脐带血中HIF-1α和NO水平。

结果：本试验中共纳入了46例妊娠病例，包括25例子痫前期病例（13例为早发性子痫前期、12例为晚发性子痫前期），同时还设立了对照组，共纳入了21例正常妊娠女性。结果发现子痫前期组较对照组相比，对照组母体血中HIF-1α水平升高，子痫前期组脐带血中NO水平升高（分别p<0.05,p<0.001）。在第二项分析中，当与对照组相比时，早发性和晚发性子痫前期组脐带血中NO水平均升高（p<0.001）。

结论：在这项研究中，我们发现与对照组相比，在子痫前期组母体血中HIF-1α水平降低，脐带血中NO水平升高。这个结果说明子痫前期患者脐带血中NO水平增加了机体对缺氧的反应性。然而，子痫前期组中较低的HIF-1α可能是由于我们目前样本含量不足所致，今后的研究中需要扩大相应的样本含量。

Keywords:

• Early onset preeclampsia
• HIF-1α
• late onset preeclampsia
• NO
• umbilical cord

Declaration of interest

The authors report no conflicts of interest. This research was supported by a research fund from Adnan Menderes University.