Institute of Maternal, Child and Adolescent Health, School of Public Health, Lanzhou University, Lanzhou, 730000, China.
Maternal and Child Health Hospital of Jingning Country, Lanzhou, 743400, China.
Placenta. 2021 Jan 1;103:16-23. doi: 10.1016/j.placenta.2020.10.005. Epub 2020 Oct 8.
To analyze the effects of the Human Chorionic Gonadotropin beta (β-hCG) and the VEGF-MEK/ERK signaling pathway on villi angiogenesis in early missed abortion.
A total of 12 cases of women with missed abortion and 12 cases of women who had induced abortion voluntarily without any disease were included in the present study. The age, pregnancy time and gestation period in the control group corresponded to the missed abortion group. Wes Simple Western system and qRT-PCR were used to detect the expression of VEGF-MEK/ERK signaling pathway related proteins and genes in villous. Radioimmunoassay and Enzyme-linked immunosorbent assay were used to detect β-hCG and VEGF levels in serum. The microvascular density (MVD) in villous tissue was analyzed by immunohistochemical staining.
The levels of β-hCG and VEGF in serum, the expression of VEGF-MEK/ERK signaling pathway and MVD in villous tissue of the missed abortion group were lower than those of the control group. In addition, compared with the control group, the layers of trophoblasts of the villous tissue in the missed abortion group became thinner significantly, the number of cells reduced, the cell structures were disorganized, and parts of the trophoblast cells were absent. Correlational analysis showed that the protein expression of ERK1/2 was positively correlated with MVD in missed abortion group.
Our results reveal that decreased production of β-hCG in early pregnant women could down-regulate the expression of VEGF-MEK/ERK signal pathway, then reduce angiogenesis and eventually leading to the abnormal angiogenesis of villous, which may be an important mechanism of missed abortion.
分析人绒毛膜促性腺激素β(β-hCG)和 VEGF-MEK/ERK 信号通路对早期稽留流产绒毛血管生成的影响。
选取稽留流产患者 12 例,自愿无病人工流产患者 12 例作为对照组。对照组的年龄、妊娠时间和妊娠周期与稽留流产组相匹配。采用 Simple Western 系统和 qRT-PCR 检测绒毛组织中 VEGF-MEK/ERK 信号通路相关蛋白和基因的表达,采用放射免疫法和酶联免疫吸附试验检测血清β-hCG 和 VEGF 水平,采用免疫组织化学染色分析绒毛组织微血管密度(MVD)。
血清β-hCG 和 VEGF 水平、绒毛组织中 VEGF-MEK/ERK 信号通路的表达和 MVD 均低于对照组。此外,与对照组相比,稽留流产组绒毛组织的滋养层细胞层明显变薄,细胞数量减少,细胞结构紊乱,部分滋养层细胞缺失。相关性分析显示,ERK1/2 蛋白表达与稽留流产组的 MVD 呈正相关。
本研究结果表明,早孕妇女β-hCG 产生减少可下调 VEGF-MEK/ERK 信号通路的表达,从而减少血管生成,最终导致绒毛血管异常,这可能是稽留流产的重要机制。