Oxygen, the Janus gas; its effects on human placental development and function.
Oxygen, the Janus gas; its effects on human placental development and function.
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DOI：
10.1111/j.1469-7580.2008.00978.x
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发表时间：
2009-07
影响因子：
2.4
通讯作者：
Burton GJ
中科院分区：
文献类型：
--
作者：
Burton GJ
地球大气中氧气的积累使得基于高能电子转移的代谢途径能够维持复杂的多细胞生物体的进化。然而，这一进步是有代价的，因为氧的高反应性带来了重大挑战，因为生物分子容易受到氧化损伤，导致潜在的功能丧失。因此，许多现存的生理系统都经过调整和稳态调节，以提供足够的氧气来满足能量需求，同时也保护细胞，特别是线粒体，免受可能导致氧化损伤的浓度过高的影响。人类胚胎所表现出的侵入性植入形式在这方面提出了特殊的挑战。在妊娠的前三个月，孕体在低氧环境中发育，有利于胚胎的器官发生以及胎盘的细胞增殖和血管生成。在怀孕后期，需要更高的氧气浓度来支持胎儿的快速生长。这种转变似乎是人类胎盘所特有的，必须安全地进行才能成功怀孕。通常，母体胎盘循环的开始是一种进行性的周围-中心现象，并且与广泛的绒毛退化形成绒毛膜相关。在流产的情况下，循环的开始既早熟又紊乱，过度的胎盘氧化应激和绒毛退化无疑会导致流产。实验和体内数据的比较表明，胎盘氧浓度的波动比单独的慢性缺氧更能刺激氧化应激的产生。胎盘氧化应激和内质网应激通过对胎盘功能和生长产生不利影响，似乎在妊娠并发症（例如宫内生长受限和先兆子痫）的病理生理学中发挥着关键作用。因此，为妊娠中期和晚期建立不可侵犯的母体血液供应是人类胎盘形成最关键的方面之一。
The accumulation of oxygen in the earth's atmosphere enabled metabolic pathways based on high-energy electron transfers that were capable of sustaining complex multicellular organisms to evolve. This advance came at a price, however, for the high reactivity of oxygen posed a major challenge as biological molecules became susceptible to oxidative damage, resulting in potential loss of function. Many extant physiological systems are therefore adapted, and homeostatically regulated, to supply sufficient oxygen to meet energy demands whilst also protecting cells, and mitochondria in particular, from excessive concentrations that could lead to oxidative damage. The invasive form of implantation displayed by the human conceptus presents particular challenges in this respect. During the first trimester, the conceptus develops in a low oxygen environment that favours organogenesis in the embryo, and cell proliferation and angiogenesis in the placenta. Later in pregnancy, higher oxygen concentrations are required to support the rapid growth of the fetus. This transition, which appears unique to the human placenta, must be negotiated safely for a successful pregnancy. Normally, onset of the maternal placental circulation is a progressive periphery-centre phenomenon, and is associated with extensive villous regression to form the chorion laeve. In cases of miscarriage, onset of the circulation is both precocious and disorganized, and excessive placental oxidative stress and villous regression undoubtedly contribute to loss of the pregnancy. Comparison of experimental and in vivo data indicates that fluctuations in placental oxygen concentration are a more powerful stimulus for the generation of oxidative stress than chronic hypoxia alone. Placental oxidative and endoplasmic reticulum stress appear to play key roles in the pathophysiology of complications of pregnancy, such as intrauterine growth restriction and preeclampsia, through their adverse impacts on placental function and growth. Establishing an inviolable maternal blood supply for the second and third trimesters is therefore one of the most crucial aspects of human placentation.
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影响因子：
6
作者：
Cindrova-Davies, Tereza;Spasic-Boskovic, Olivera;Jauniaux, Eric;Charnock-Jones, D. Stephen;Burton, Graham J.
通讯作者：
Burton, Graham J.
影响因子：
2.4
作者：
Charnock-Jones, DS
通讯作者：
Charnock-Jones, DS
影响因子：
5.8
作者：
Frendo, JL;Vidaud, M;Evain-Brion, D
通讯作者：
Evain-Brion, D
影响因子：
3.8
作者：
Carter, AM
通讯作者：
Carter, AM
影响因子：
3.8
作者：
Ali, KZM
通讯作者：
Ali, KZM