Downregulating Notch-1-induced cytostatic and anti-angiogenic effects on trophoblast cells is associated with early spontaneous abortion

作者：Yu, Na; Tan, Yingchun; Zhang, Zhiwei; Liu, Zonghua; Wang, Ting; Guo, Wei^*

来源：International Journal of Clinical and Experimental Pathology, 2016, 9(7): 7255-7265.

• Early spontaneous abortion
• villi
• trophoblast cells
• Notch-1
• proliferation
• VEGF

Notch signaling pathway is essential for the migration and invasion of trophoblast cells. However, limited attention has been directed towards the contribution of Notch-1 to the viability and angiogenesis of trophoblast cells during early spontaneous abortion (ESA). This study aimed to explore the effects of Notch-1 on the proliferation, apoptosis, and angiogenesis of trophoblast cells in vivo and in vitro. 30 cases of villi tissues from ESA patients and 30 cases from induced abortion patients as healthy control were collected. HE staining analysis detected an obvious decline of trophoblast cells in the villi of patients with ESA. The significantly decreased expressions of VEGF, VEGFR1 and Notch-1 along with the notably elevated expressions of VEGFR2 and DLL4 were observed in the villi of ESA patients compared with induced abortion patients (P < 0.05), as evidenced by Real-time PCR, western blot and immunohistochemical assay. Further MTT assay demonstrated that the growth of cultured trophoblast cells was appeared to be reduced in a dose-dependent manner after inhibiting the expression of Notch-1 by DAPT (P < 0.001). Flow cytometry analysis showed that DAPT dose-dependently enhanced the apoptosis of trophoblast cells (P < 0.01). Suppressed Notch-1 activity also resulted in the downregulation of VEGFR1 and upregulation of VEGFR2 in trophoblast cells (P < 0.001). Overall, our data indicated that downregulating Notch-1-induced cytostatic and anti-angiogenic effects was mediated by the inhibited proliferation, increased apoptosis and disrupted intrinsic VEGF/VEGFRs balances in trophoblast cells, which is closely associated with ESA. Therefore, Notch-1 may be further assessed as a potential target for the treatment of ESA.

• 出版日期2016
• 单位山东省千佛山医院; 山东大学