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. 2013 Aug 9;8(8):e70667.
doi: 10.1371/journal.pone.0070667. eCollection 2013.

Association of Dll4/notch and HIF-1a -VEGF signaling in the angiogenesis of missed abortion

Yan Fang  1 , Shuang Yu, Yuyan Ma, Ping Sun, Daoxin Ma, Chunyan Ji, Beihua Kong
Affiliations

Association of Dll4/notch and HIF-1a -VEGF signaling in the angiogenesis of missed abortion

Yan Fang et al. PLoS One. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Analysis of Dll4/Notch1 and HIF-1a-VEGF signaling molecules using Real-time RT-PCR.
A. VEGF expression was significantly down-regulated in missed abortion compared with induced abortion. B, C, D. VEGFR1, Notch1 and HIF-1a expression were significantly up-regulated in missed abortion compared with induced abortion. E, F. VEGFR2 and Dll4 expressions were higher in missed abortion than in induced abortion, whereas no statistical difference was observed.
Figure 2
Figure 2. Analysis of Dll4 using immunohistochemistry.
The protein expression of Dll4 was up-regulated in missed abortion (A) than that in induced abortion (B).
Figure 3
Figure 3. Correlation analysis in missed abortion.
A. the expression of VEGFR1 positively correlated with Notch1 in missed abortion; B. VEGFR2 expression positively correlated with Notch1 in missed abortion; C. Dll4 expression positively correlated with Notch1 in missed abortion; D. HIF-1a positively correlated with Notch1 in missed abortion; E. HIF-1a was closely negatively correlated with VEGF in missed abortion.
Figure 4
Figure 4. Correlation analysis in induced abortion.
A.VEGF positively correlated withVEGFR1. B.VEGF expression close positively correlated with VEGFR2. C.VEGFR1 expression close positively correlated with VEGFR2. D-,G.Dll4 positively correlated with VEGF,VEGFR1, VEGFR2, Notch1. H,I. HIF-1a positively correlated with VEGFR2 or Dll4.
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