Chang Ching-Wen, Wakeland Anna K, Parast Mana M
Department of PathologyUniversity of California San Diego, La Jolla, California, USA.
Sanford Consortium for Regenerative MedicineUniversity of California San Diego, La Jolla, California, USA.
J Endocrinol. 2018 Jan;236(1):R43-R56. doi: 10.1530/JOE-17-0402.
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, proliferate, forming the cytotrophoblastic shell, the early placenta. The cytotrophoblasts (CTBs) 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, the nutrient sensor mTOR and the endoplasmic reticulum stress-induced unfolded protein response 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.
早期胚胎的发育在低氧张力条件下进行。在这种情况下，胚胎着床，囊胚的外层滋养外胚层增殖，形成细胞滋养层壳，即早期胎盘。细胞滋养层细胞（CTB）是胎盘所谓的上皮“干细胞”，根据它们接收到的信号，可分化为绒毛外滋养层细胞（EVT）或合体滋养层细胞（STB）。EVT将胎盘锚定在子宫壁上，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。STB通过CTB融合产生，分泌维持妊娠所需的激素，并形成一个屏障，营养物质和气体可通过该屏障进行交换。大部分EVT分化发生在孕早期，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。这些条件会影响众多信号通路，包括通过缺氧诱导因子、营养传感器mTOR和内质网应激诱导的未折叠蛋白反应通路起作用的信号通路。已知这些通路参与胎盘发育和疾病，甚至已确定特定成分直接参与谱系特异性滋养层细胞分化。然而，关于缺氧在滋养层细胞分化中的作用，尤其是在EVT方面，仍存在很多争议。本综述总结了此前关于该主题的研究，旨在整合这些结果并得出结论，以解决部分争议，但同时也指出仍需进一步研究的领域。
