Aye Irving L M H, Tong Stephen, Charnock-Jones D Stephen, Smith Gordon C S
Department of Obstetrics and Gynaecology, University of Cambridge, National Institute for Health and Care Research Cambridge Comprehensive Biomedical Research Centre, Cambridge, United Kingdom.
Loke Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Physiol Rev. 2025 Oct 1;105(4):2305-2376. doi: 10.1152/physrev.00039.2024. Epub 2025 Jun 11.
The placenta performs many key tasks that are essential for the healthy growth and development of the human fetus. Placental dysfunction has multiple manifestations, but they share the common property of lacking a mechanistic understanding of etiology. The clinical consequences of placental dysfunction are a major determinant of the global burden of disease. Currently, the primary clinical method for assessing placental function is ultrasonic Doppler flow velocimetry of the umbilical and uterine arteries. More recently, some biomarkers have emerged that can predict or diagnose placentally related complications of pregnancy. However, methods for identifying and characterizing placental dysfunction have developed relatively little over the last 20 years and perform poorly, and there remains an absence of disease-modifying therapies targeted at the placenta. Understanding disease mechanisms is made more difficult due to the profound differences in pregnancy and placentation comparing humans and the most commonly used laboratory animals, limiting the utility of animal models. The use of omics methods in human samples may yield progress: omics analyses of maternal blood show promise in identifying better predictors of disease, and single-cell analyses, including spatial omics of healthy and abnormal placentas, could identify therapeutic targets. Limitations in cellular models of the placenta have been significantly overcome in the last 5 to 10 years by the development of human cell models, including human trophoblast stem cells and organoids, and the use of these model systems may allow hypothesis testing experiments in a more clinically relevant context than animal models or immortalized cell lines.
胎盘执行许多对人类胎儿健康生长和发育至关重要的关键任务。胎盘功能障碍有多种表现形式，但它们都有一个共同特点，即对病因缺乏机制性的理解。胎盘功能障碍的临床后果是全球疾病负担的主要决定因素。目前，评估胎盘功能的主要临床方法是脐动脉和子宫动脉的超声多普勒血流测速。最近，一些生物标志物出现了，它们可以预测或诊断与胎盘相关的妊娠并发症。然而，在过去20年里，识别和表征胎盘功能障碍的方法发展相对较少，效果不佳，而且仍然缺乏针对胎盘的疾病改善疗法。由于人类与最常用的实验动物在妊娠和胎盘形成方面存在巨大差异，理解疾病机制变得更加困难，这限制了动物模型的实用性。在人类样本中使用组学方法可能会取得进展：对母体血液进行组学分析有望识别出更好的疾病预测指标，单细胞分析，包括对健康和异常胎盘的空间组学分析，可能会识别出治疗靶点。在过去5到10年里，通过人类细胞模型的发展，包括人类滋养层干细胞和类器官，胎盘细胞模型的局限性已得到显著克服，使用这些模型系统可能比动物模型或永生化细胞系在更具临床相关性的背景下进行假设检验实验。
