Association of Dll4/notch and HIF-1a -VEGF signaling in the angiogenesis of missed abortion.
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.
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Ji'nan, Shandong, China.
Yan
Y
Fang
Shuang
S
Yu
Yuyan
Y
Ma
Ping
P
Sun
Daoxin
D
Ma
Chunyan
C
Ji
Beihua
B
Kong
D000028:Abortion, Induced; D000030:Abortion, Missed / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D002135:Calcium-Binding Proteins; D016022:Case-Control Studies; D002824:Chorionic Villi / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005313:Fetal Death / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D009389:Neovascularization, Pathologic; D011247:Pregnancy; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A