Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge, United Kingdom; Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom; National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, University of Cambridge, United Kingdom.
Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge, United Kingdom; National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, University of Cambridge, United Kingdom.
Am J Obstet Gynecol. 2022 Feb;226(2S):S928-S944. doi: 10.1016/j.ajog.2020.11.005. Epub 2020 Nov 13.
The placenta is a highly metabolically active organ fulfilling the bioenergetic and biosynthetic needs to support its own rapid growth and that of the fetus. Placental metabolic dysfunction is a common occurrence in preeclampsia although its causal relationship to the pathophysiology is unclear. At the outset, this may simply be seen as an "engine out of fuel." However, placental metabolism plays a vital role beyond energy production and is linked to physiological and developmental processes. In this review, we discuss the metabolic basis for placental dysfunction and propose that the alterations in energy metabolism may explain many of the placental phenotypes of preeclampsia such as reduced placental and fetal growth, redox imbalance, oxidative stress, altered epigenetic and gene expression profiles, and the functional consequences of these aberrations. We propose that placental metabolic reprogramming reflects the dynamic physiological state allowing the tissue to adapt to developmental changes and respond to preeclampsia stress, whereas the inability to reprogram placental metabolism may result in severe preeclampsia phenotypes. Finally, we discuss common tested and novel therapeutic strategies for treating placental dysfunction in preeclampsia and their impact on placental energy metabolism as possible explanations into their potential benefits or harm.
胎盘是一个高度代谢活跃的器官，满足自身快速生长和胎儿生长的生物能量和生物合成需求。尽管胎盘代谢功能障碍与病理生理学的因果关系尚不清楚，但子痫前期中这种情况很常见。起初，这可能仅仅被视为“发动机没有燃料”。然而，胎盘代谢在能量产生之外发挥着至关重要的作用，并与生理和发育过程有关。在这篇综述中，我们讨论了胎盘功能障碍的代谢基础，并提出能量代谢的改变可以解释子痫前期的许多胎盘表型，如胎盘和胎儿生长减少、氧化还原失衡、氧化应激、表观遗传和基因表达谱改变，以及这些异常的功能后果。我们提出，胎盘代谢重编程反映了动态的生理状态，使组织能够适应发育变化并对子痫前期应激做出反应，而胎盘代谢不能重编程可能导致严重的子痫前期表型。最后，我们讨论了治疗子痫前期胎盘功能障碍的常用测试和新型治疗策略及其对胎盘能量代谢的影响，这些可能解释了它们的潜在益处或危害。
