Centre for Trophoblast Research, Department of Physiology Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK.
J Anat. 2009 Jul;215(1):27-35. doi: 10.1111/j.1469-7580.2008.00978.x. Epub 2008 Oct 13.
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.
氧气在地球大气中的积累使基于高能电子转移的代谢途径得以发展，从而使复杂的多细胞生物得以进化。然而，这一进步是有代价的，因为氧气的高反应性对生物分子构成了重大挑战，使它们容易受到氧化损伤，从而导致潜在的功能丧失。因此，许多现存的生理系统都适应了这种情况，并通过体内平衡调节来供应足够的氧气以满足能量需求，同时保护细胞，特别是线粒体免受可能导致氧化损伤的高浓度氧气的影响。人类胚胎所表现出的侵袭性植入形式在这方面带来了特殊的挑战。在妊娠的头三个月，胚胎在低氧环境中发育，有利于胚胎器官发生，以及胎盘中的细胞增殖和血管生成。妊娠后期，需要更高的氧气浓度来支持胎儿的快速生长。这种过渡似乎是人类胎盘所特有的，必须安全地过渡，才能实现成功的妊娠。通常，母体胎盘循环的开始是一个渐进的从外周到中心的现象，伴随着广泛的绒毛退化形成绒毛膜叶。在流产的情况下，循环的开始是既早熟又紊乱的，过度的胎盘氧化应激和绒毛退化无疑导致了妊娠的丧失。实验和体内数据的比较表明，胎盘氧浓度的波动比单纯慢性缺氧更能刺激氧化应激的产生。胎盘氧化和内质网应激似乎在妊娠并发症的病理生理学中发挥关键作用，如宫内生长受限和子痫前期，通过对胎盘功能和生长的不利影响。因此，为妊娠的第二和第三个三个月建立不可侵犯的母体血液供应是人类胎盘形成的最关键方面之一。
