Oxygen and placental development; parallels and differences with tumour biology
Oxygen and placental development; parallels and differences with tumour biology
复制标题
DOI：
10.1016/j.placenta.2017.01.130
复制
发表时间：
2017-08-01
期刊：
影响因子：
3.8
通讯作者：
Murray, Andrew J.
中科院分区：
文献类型：
--
作者：
Burton, Graham J.;Jauniaux, Eric;Murray, Andrew J.
人类胎盘形成包括孕体侵入子宫壁，并建立来自母体螺旋动脉的血液供应。因此，胎盘被比作恶性肿瘤，尽管是一种高度调控的肿瘤。氧气在控制胎盘发育和肿瘤行为方面起着重要作用。在胎盘中，早期发育发生在生理低氧环境中，其经历了一个过渡期，在第一个三个月结束时开始完全的母体动脉循环。相比之下，在肿瘤中，随着肿块的生长超过其血液供应，通常会出现进行性缺氧。早期胎盘组织和肿瘤细胞都表现出高增殖率，支持这些增殖所需的能量主要来自糖酵解。糖酵解在胎盘组织中通过多元醇途径吡啶核苷酸的再氧化来维持，而在肿瘤中存在发酵成乳酸的瓦尔堡代谢。在这两种情况下，依赖于糖酵解而不是氧化磷酸化保留了碳骨架，这些碳骨架可用于合成核苷酸、细胞膜和细胞器，否则将以二氧化碳的形式排出。在胎盘中，这种依赖也可能保护胚胎免受自由基介导的畸形发生。两组组织内的局部氧梯度可能会影响细胞行为。特别是，它们可以诱导上皮-间质转化，促进胎盘中的绒毛外滋养层浸润和肿瘤转移。对这两种情况的进一步研究可能会为这些对比但相似的细胞生物学领域提供新的有益见解。(C)2017爱思唯尔有限公司版权所有
Human placentation involves the invasion of the conceptus into the wall of the uterus, and establishment of a blood supply from the maternal spiral arteries. The placenta has therefore been likened to a malignant tumour, albeit a highly regulated one. Oxygen plays an important role in controlling both placental development and tumour behaviour. In the placenta, early development takes place in a physiological low oxygen environment, which undergoes a transition with onset of the full maternal arterial circulation towards the end of the first trimester. By comparison, in tumours there is often a progressive hypoxia as the mass outgrows its blood supply. Both early placental tissues and tumour cells show high rates of proliferation, and the energy required to support these comes principally from glycolysis. Glycolysis is maintained in placental tissues by reoxidation of pyridine nucleotides through the polyol pathways, whereas in tumours there is fermentation to lactate, Warburg metabolism. In both cases, the reliance on glycolysis rather than oxidative phosphorylation preserves carbon skeletons that can be utilised in the synthesis of nucleotides, cell membranes and organelles, and that would otherwise be excreted as carbon dioxide. In the placenta, this reliance may also protect the embryo from free radical-mediated teratogenesis. Local oxygen gradients within both sets of tissues may influence the cell behaviour. In particular, they may induce an epithelial-mesenchymal transition, promoting extravillous trophoblast invasion in the placenta and metastasis in a tumour. Further investigations into the two scenarios may provide new insights of benefit to these contrasting, but similar, fields of cellular biology. (C) 2017 Elsevier Ltd. All rights reserved.