Reproductive and Vascular Biology Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Reproduction. 2019 Nov;158(5):389-397. doi: 10.1530/REP-19-0133.
Uterine spiral arteries undergo remodelling in normal pregnancy, with replacement of the musculoelastic arterial media by fibrinoid containing extravillous trophoblast cells. Deficient spiral artery remodelling is associated with several adverse pregnancy outcomes. Although there are distinct components of spiral artery remodelling, assessment is subjective and often based on an overall impression of morphology. We aimed to develop a quantitative approach for assessment of uterine spiral artery remodelling. Placental bed biopsies were immunostained using smooth muscle markers, digital images of spiral arteries were captured and Adobe Photoshop was used to analyse positive immunostaining. The method was then used to investigate variation in the same vessel at different levels within a paraffin block, and the effect of parity, pre-eclampsia or miscarriage on vascular smooth muscle cell content. Results were also compared with a more subjective morphology-based assessment system. There was good intra- and interobserver agreement and the method correlated well with the more subjective assessment system. There was an overall reduction in vascular smooth muscle, as detected by caldesmon 1 (h-caldesmon) immunopositivity, with increasing gestational age from 8 weeks to term. A previous pregnancy did not affect the amount of spiral artery smooth muscle. Comparison of pre-eclampsia and late miscarriage samples with controls of the appropriate gestational age demonstrated increased medial smooth muscle in pathological samples. This technique provides a simple, rapid, reproducible and inexpensive approach to quantitative assessment of spiral artery remodelling in normal and pathological human pregnancy, a process which although fundamental for successful pregnancy, is still incompletely understood.
正常妊娠时,子宫螺旋动脉发生重塑,其中富含纤维蛋白的绒毛外滋养层细胞取代了肌弹性动脉中层。螺旋动脉重塑不足与多种不良妊娠结局有关。尽管螺旋动脉重塑有明显的组成部分,但评估是主观的,通常基于形态的整体印象。我们旨在开发一种评估子宫螺旋动脉重塑的定量方法。使用平滑肌标志物对胎盘床活检进行免疫染色,捕获螺旋动脉的数字图像,并使用 Adobe Photoshop 分析阳性免疫染色。然后,该方法用于研究石蜡块内同一血管在不同水平上的变化,以及经产妇、子痫前期或流产对血管平滑肌细胞含量的影响。结果还与更主观的基于形态的评估系统进行了比较。该方法具有良好的观察者内和观察者间一致性,并且与更主观的评估系统相关性良好。随着妊娠龄从 8 周增加到足月,钙调蛋白 1(h-caldesmon)免疫阳性检测到的血管平滑肌总体减少。既往妊娠不会影响螺旋动脉平滑肌的数量。与适当妊娠龄的对照组相比,子痫前期和晚期流产样本的比较显示,病理性样本的中膜平滑肌增加。该技术为正常和病理性人类妊娠中螺旋动脉重塑的定量评估提供了一种简单、快速、可重复且经济实惠的方法,尽管这是成功妊娠的基础,但仍不完全了解这一过程。