Redman C W, Sargent I L, Staff A C
The John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
The John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
Placenta. 2014 Feb;35 Suppl:S20-5. doi: 10.1016/j.placenta.2013.12.008. Epub 2014 Jan 11.
Incomplete spiral artery remodelling is the first of two stages of pre-eclampsia, typically of early onset. The second stage comprises dysregulated uteroplacental perfusion and placental oxidative stress. Oxidatively stressed syncytiotrophoblast (STB) over-secretes proteins that perturb maternal angiogenic balance and are considered to be pre-eclampsia biomarkers. We propose that, in addition and more fundamentally, these STB-derived proteins are biomarkers of a cellular (STB) stress response, which typically involves up-regulation of some proteins and down-regulation of others (positive and negative stress proteins respectively). Soluble vascular growth factor receptor-1 (sVEGFR-1) and reduced growth factor (PlGF) then exemplify positive and negative STB stress response proteins in the maternal circulation. Uncomplicated term pregnancy is associated with increasing sVEGFR-1 and decreasing PlGF, which can be interpreted as evidence of increasing STB stress. STB pathology, at or after term (for example focal STB necrosis) demonstrates this stress, with or without pre-eclampsia. We review the evidence that when placental growth reaches its limits at term, terminal villi become over-crowded with diminished intervillous pore size impeding intervillous perfusion with increasing intervillous hypoxia and STB stress. This type of STB stress has no antecedent pathology, so the fetuses are well-grown, as typifies late onset pre-eclampsia, and prediction is less effective than for the early onset syndrome because STB stress is a late event. In summary, abnormal placental perfusion and STB stress contribute to the pathogenesis of early and late onset pre-eclampsia. But the former has an extrinsic cause - poor placentation, whereas the latter has an intrinsic cause, 'microvillous overcrowding', as placental growth reaches its functional limits. This model explains important features of late pre-eclampsia and raises questions of how antecedent medical risk factors such as chronic hypertension affect early and late sub-types of the syndrome. It also implies that all pregnant women may be destined to get pre-eclampsia but spontaneous or induced delivery averts this outcome in most instances.
不完全螺旋动脉重塑是子痫前期两个阶段中的第一个阶段，通常为早发型。第二阶段包括子宫胎盘灌注失调和胎盘氧化应激。氧化应激的合体滋养层细胞（STB）过度分泌扰乱母体血管生成平衡的蛋白质，这些蛋白质被认为是子痫前期的生物标志物。我们提出，除此之外且更根本的是，这些源自STB的蛋白质是细胞（STB）应激反应的生物标志物，这种应激反应通常涉及一些蛋白质的上调和其他蛋白质的下调（分别为正向和负向应激蛋白）。可溶性血管生长因子受体-1（sVEGFR-1）和胎盘生长因子（PlGF）随后分别作为母体循环中正向和负向STB应激反应蛋白的例证。足月正常妊娠与sVEGFR-1升高和PlGF降低相关，这可被解释为STB应激增加的证据。足月时或足月后STB的病理变化（例如局灶性STB坏死）显示了这种应激，无论是否伴有子痫前期。我们回顾了相关证据，即当足月时胎盘生长达到极限，终末绒毛会过度拥挤，绒毛间隙孔径减小，阻碍绒毛间隙灌注，导致绒毛间隙缺氧和STB应激增加。这种类型的STB应激没有前期病理变化，因此胎儿生长良好，这是晚发型子痫前期的典型表现，并且由于STB应激是晚期事件，所以预测效果不如早发型综合征。总之，胎盘灌注异常和STB应激促成了早发型和晚发型子痫前期的发病机制。但前者有外在原因——胎盘着床不良，而后者有内在原因，即“微绒毛过度拥挤”，因为胎盘生长达到了其功能极限。该模型解释了晚发型子痫前期的重要特征，并引发了诸如慢性高血压等前期医学风险因素如何影响该综合征的早发型和晚发型亚型的问题。这也意味着所有孕妇可能注定会患子痫前期，但在大多数情况下，自然分娩或引产可避免这种结果。
