Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Ji'nan, Shandong, China.
PLoS One. 2013 Aug 9;8(8):e70667. doi: 10.1371/journal.pone.0070667. eCollection 2013.
Dll4/Notch and HIF-1a-VEGF have been shown to play an important role during angiogenesis, but there are no data about their roles and association in missed abortion. In this study, we investigated the association of Dll4/Notch and HIF-1a-VEGF signaling in missed abortion.
Women with missed abortion (n=27) and healthy controls (n=26) were included in the study. Real-time Reverse Transcription-PCR Analyses (RT-PCR) was used to analyze the mRNA levels of Dll4/Notch and HIF-1a-VEGF signaling molecules. The protein level for Dll4 was measured by immunohistochemistry.
Compared with induced abortion, the expression of VEGF was statistically reduced while the level of VEGFR1 and Notch1 was significantly up-regulated in missed abortion. Though other molecules (VEGFR2 and Dll4) were marginally higher in missed abortion, no statistical difference was observed. The expression of HIF-1a was significantly up-regulated, and close negatively correlated with VEGF in missed abortion. Both in induced abortion and missed abortion, Dll4 was positively correlated with Notch1.
The early pregnancy is in a hypoxic environment, this may encourage the angiogenesis, but severe hypoxic may inhibit the angiogenesis. Aberrant Dll4/Notch and HIF-1a-VEGF signaling may have a role in missed abortion.
Dll4/Notch 和 HIF-1a-VEGF 在血管生成中起着重要作用，但关于它们在稽留流产中的作用和关联尚无数据。本研究旨在探讨 Dll4/Notch 和 HIF-1a-VEGF 信号通路在稽留流产中的关联。
纳入稽留流产患者（n=27）和健康对照组（n=26）。采用实时逆转录聚合酶链反应（RT-PCR）分析 Dll4/Notch 和 HIF-1a-VEGF 信号分子的 mRNA 水平。免疫组织化学法测定 Dll4 蛋白水平。
与人工流产相比，稽留流产组 VEGF 表达水平显著降低，而 VEGFR1 和 Notch1 水平显著升高。虽然稽留流产组其他分子（VEGFR2 和 Dll4）略有升高，但无统计学差异。HIF-1a 的表达显著升高，与稽留流产中 VEGF 呈负相关。在人工流产和稽留流产中，Dll4 与 Notch1 均呈正相关。
早期妊娠处于低氧环境中，这可能会促进血管生成，但严重的低氧可能会抑制血管生成。异常的 Dll4/Notch 和 HIF-1a-VEGF 信号通路可能在稽留流产中发挥作用。
