Yamashita Michiko, Kumasawa Keiichi, Nakamura Hitomi, Kimura Tadashi
Department of Obstetrics and Gynecology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Biochem Biophys Res Commun. 2018 Feb 19;496(4):1243-1249. doi: 10.1016/j.bbrc.2018.01.180. Epub 2018 Jan 31.
Placenta previa is an abnormality in which the placenta covers the internal uterine os, and it can cause serious morbidity and mortality in both mother and fetus due to catastrophic hemorrhage. Some pregnant women recover from placenta previa due to a phenomenon called "migration." However, the mechanism of "migration" of the placenta has not been elucidated.
Human placentas were collected from patients with placenta previa and those with no abnormal placentation (control). A microarray analysis was performed to detect the genes up- or down-regulated only in the caudal part in the previa group. Specific mRNA expression was evaluated using real-time quantitative reverse transcription PCR (qRT-PCR). Unilateral uterine artery ablation of 8.5 dpc mice was performed to reproduce the reduction of placental blood supply, and weights of the placentas and fetuses were evaluated in 18.5 dpc. Specific mRNA expression was also evaluated in mice placentas.
According to the result of the microarray analysis, we focused on soluble fms-like tyrosine kinase-1 (sFLT-1) and hypoxia-inducible factor-1 (HIF-1) alpha. The sFLT-1 expression level is locally high in the caudal part of the human placenta in patients with placenta previa. In mice experiments, the weights of the placentas and fetuses were significantly smaller in the ablation side than those in the control side, and the sFlt-1 expression level was significantly higher in the ablation side than in the control side.
Our study suggests that "migration" of the placenta is derived from placental degeneration at the caudal part of the placenta, and sFlt-1 plays a role in this placental degeneration.
前置胎盘是一种胎盘覆盖子宫内口的异常情况，由于灾难性出血，它可导致母亲和胎儿出现严重的发病率和死亡率。一些孕妇因一种称为“迁移”的现象从前置胎盘中恢复。然而，胎盘“迁移”的机制尚未阐明。
从前置胎盘患者和无胎盘异常的患者（对照）中收集人胎盘。进行微阵列分析以检测仅在前置胎盘组尾侧部分上调或下调的基因。使用实时定量逆转录PCR（qRT-PCR）评估特定mRNA表达。对8.5天胚龄的小鼠进行单侧子宫动脉消融以重现胎盘血液供应的减少，并在18.5天胚龄时评估胎盘和胎儿的重量。还对小鼠胎盘的特定mRNA表达进行了评估。
根据微阵列分析结果，我们重点关注可溶性fms样酪氨酸激酶-1（sFLT-1）和缺氧诱导因子-1（HIF-1）α。前置胎盘患者人胎盘尾侧部分的sFLT-1表达水平局部较高。在小鼠实验中，消融侧胎盘和胎儿的重量明显小于对照侧，消融侧的sFlt-1表达水平明显高于对照侧。
我们的研究表明，胎盘的“迁移”源于胎盘尾侧部分的胎盘退化，并且sFlt-1在这种胎盘退化中起作用。
