Enhanced Placental Mitochondrial Respiration in Tibetan Women at High Altitude
Keywords：Tibetan; high altitude adaptation; hypoxia; mitochondria respiration; placenta
关键词：藏; 高海拔适应； 缺氧; 线粒体呼吸； 胎盘
作者：Liu H, Tenzing N, van Patot MT, Qile M, Ge RL, Wuren T
出版期刊：《Frontiers in Physiology》 2021/7/14
Living at high altitudes is extremely challenging as it entails exposure to hypoxia, low temperatures, and high levels of UV radiation. However, the Tibetan population has adapted to such conditions on both a physiological and genetic level over 30,000-40,000 years. It has long been speculated that fetal growth restriction is caused by abnormal placental development. We previously demonstrated that placentas from high-altitude Tibetans were protected from oxidative stress induced by labor compared to those of European descent. However, little is known about how placental mitochondria change during high-altitude adaptation. In this study, we aimed to uncover the mechanism of such adaptation by studying the respiratory function of the placental mitochondria of high-altitude Tibetans, lower-altitude Tibetans, and lower-altitude Chinese Han. We discovered that mitochondrial respiration was greater in high-altitude than in lower-altitude Tibetans in terms of OXPHOS via complexes I and I+II, ETSmax capacity, and non-phosphorylating respiration, whereas non-ETS respiration, LEAK/ETS, and OXPHOS via complex IV did not differ. Respiration in lower-altitude Tibetans and Han was similar for all tested respiratory states. Placentas from high-altitude Tibetan women were protected from acute ischemic/hypoxic insult induced by labor, and increased mitochondrial respiration may represent an acute response that induces mitochondrial adaptations.
生活在高海拔地区极具挑战性，因为它需要暴露在缺氧、低温和高水平的紫外线辐射中。然而，藏族人口在 30,000 至 40,000 年的生理和遗传水平上已经适应了这种条件。长期以来一直推测胎儿生长受限是由于胎盘发育异常所致。我们之前证明，与欧洲血统的胎盘相比，来自高海拔西藏人的胎盘可以免受劳动引起的氧化应激。然而，关于高海拔适应过程中胎盘线粒体的变化知之甚少。在这项研究中，我们旨在通过研究高海拔藏族、低海拔藏族和低海拔汉族胎盘线粒体的呼吸功能来揭示这种适应的机制。我们发现高海拔地区的线粒体呼吸比低海拔西藏人的线粒体呼吸在通过复合物 I 和 I+II 的 OXPHOS、ETSmax 容量和非磷酸化呼吸方面更大，而非 ETS 呼吸、LEAK/ETS 和 OXPHOS通过复杂的 IV 没有不同。对于所有测试的呼吸状态，低海拔藏族和汉族的呼吸相似。来自高海拔西藏妇女的胎盘免受分娩引起的急性缺血/缺氧损伤，线粒体呼吸增加可能代表诱导线粒体适应的急性反应。