Trophoblast lineage specification, differentiation and their regulation by oxygen tension.
Trophoblast lineage specification, differentiation and their regulation by oxygen tension.
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DOI：
10.1530/joe-17-0402
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Parast MM
中科院分区：
文献类型：
--
作者：
Chang CW;Wakeland AK;Parast MM
早期胚胎的发育是在低氧环境下进行的。在这样的条件下，胚胎植入和滋养外胚层（胚泡的外层）增殖，形成细胞滋养层壳（早期胎盘）。细胞滋养层细胞（CTB）是胎盘的所谓上皮“干细胞”，其取决于它们接收的信号，可以分化成绒毛外滋养层细胞（EVT）或合体滋养层细胞（STB）。EVT将胎盘锚在子宫壁上，并重塑母体螺旋小动脉，以便为生长中的胎儿提供充足的血液供应。STBs通过CTB融合产生，分泌维持妊娠所必需的激素，并形成营养和气体交换可以发生的屏障。大部分EVT分化发生在妊娠早期，在母体动脉血流进入胎盘绒毛间隙之前，因此处于低氧张力下。这些条件影响许多信号传导途径，包括通过缺氧诱导因子（HIF）、营养传感器mTOR和内质网（ER）应激诱导的未折叠蛋白反应（UPR）途径起作用的那些。已知这些通路参与胎盘发育和疾病，并且特定组分甚至已被鉴定为直接参与谱系特异性滋养层分化。然而，围绕缺氧在滋养层分化中的作用，特别是EVT，仍存在许多争议。本文综述了以往关于这一主题的研究，目的是整合这些结果，并综合解决一些争议的结论，但也指出了需要进一步调查的剩余领域。
Development of the early embryo takes place under low oxygen tension. Under such conditions, the embryo implants and the trophectoderm, the outer layer of blastocyst, proliferates, forming the cytotrophoblastic shell, the early placenta. The cytotrophoblast (CTB) are the so-called epithelial “stem cells” of the placenta, which, depending on the signals they receive, can differentiate into either extravillous trophoblast (EVT) or syncytiotrophoblast (STB). EVTs anchor the placenta to the uterine wall and remodel maternal spiral arterioles in order to provide ample blood supply to the growing fetus. STBs arise through CTB fusion, secrete hormones necessary for pregnancy maintenance, and form a barrier across which nutrient and gas exchange can take place. The bulk of EVT differentiation occurs during the first trimester, before the onset of maternal arterial blood flow into the intervillous space of the placenta, and thus under low oxygen tension. These conditions affect numerous signaling pathways, including those acting through hypoxia-inducible factor (HIF), the nutrient sensor mTOR, and the endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) pathway. These pathways are known to be involved in placental development and disease, and specific components have even been identified as directly involved in lineage-specific trophoblast differentiation. Nevertheless, much controversy surrounds the role of hypoxia in trophoblast differentiation, particularly with EVT. This review summarizes previous studies on this topic, with the intent of integrating these results and synthesizing conclusions that resolve some of the controversy, but then also pointing to remaining areas which require further investigation.