Dumollard R, Carroll J, Duchen M R, Campbell K, Swann K
Laboratoire de Biologie du Développement, UMR 7009, Station Zoologique, 06230 Villefranche sur Mer, France.
Semin Cell Dev Biol. 2009 May;20(3):346-53. doi: 10.1016/j.semcdb.2008.12.013.
Mitochondria play a central and multifaceted role in the mammalian egg and early embryo, contributing to many different aspects of early development. While the contribution of mitochondria to energy production is fundamental, other roles for mitochondria are starting to emerge. Mitochondria are central to intracellular redox metabolism as they produce reactive oxygen species (ROS, the mediators of oxidative stress) and they can generate TCA cycle intermediates and reducing equivalents that are used in antioxidant defence. A high cytosolic lactate dehydrogenase activity coupled with dynamic levels of cytosolic pyruvate is responsible for a very dynamic intracellular redox state in the oocyte and embryo. Mammalian embryos have a low glucose metabolism during the earliest stages of development, as both glycolysis and the pentose phosphate pathway are suppressed. The mitochondrial TCA cycle is therefore the major source of reducing equivalents in the cytosol so that any change in mitochondrial function in the embryo will be reflected in changes in the intracellular redox state. In the mouse, the metabolic substrates used by the oocyte and early embryo each have a different impact on the intracellular redox state. Pyruvate which oxidises the cytosolic redox state, acts as an energetic and redox substrate whereas lactate, which reduces the cytosolic redox state, acts only as a redox substrate. Mammalian early embryos are very sensitive to oxidative stress which can cause permanent developmental arrest before zygotic genome activation and apoptosis in the blastocyst. The oocyte stockpiles antioxidant defence for the early embryo to cope with exogenous and endogenous oxidant insults arising during early development. Mitochondria provide ATP for glutathione (GSH) production during oocyte maturation and also participate in the regeneration of NADPH and GSH during early development. Finally, a number of pathological conditions or environmental insults impair early development by altering mitochondrial function, illustrating the centrality of mitochondrial function in embryo development.
线粒体在哺乳动物卵子和早期胚胎中发挥着核心且多方面的作用，对早期发育的许多不同方面都有贡献。虽然线粒体对能量产生的贡献至关重要，但线粒体的其他作用也开始显现。线粒体是细胞内氧化还原代谢的核心，因为它们产生活性氧（ROS，氧化应激的介质），并且可以生成用于抗氧化防御的三羧酸循环中间体和还原当量。高细胞质乳酸脱氢酶活性与细胞质丙酮酸的动态水平相结合，导致卵母细胞和胚胎中细胞内氧化还原状态非常动态。哺乳动物胚胎在发育的最早阶段葡萄糖代谢较低，因为糖酵解和磷酸戊糖途径均受到抑制。因此，线粒体三羧酸循环是细胞质中还原当量的主要来源，以至于胚胎中线粒体功能的任何变化都会反映在细胞内氧化还原状态的变化中。在小鼠中，卵母细胞和早期胚胎使用的代谢底物对细胞内氧化还原状态各有不同影响。氧化细胞质氧化还原状态的丙酮酸，既是能量和氧化还原底物，而还原细胞质氧化还原状态的乳酸，仅作为氧化还原底物。哺乳动物早期胚胎对氧化应激非常敏感，氧化应激可导致合子基因组激活前的永久性发育停滞以及囊胚期的细胞凋亡。卵母细胞为早期胚胎储备抗氧化防御，以应对早期发育过程中产生的外源性和内源性氧化剂损伤。线粒体在卵母细胞成熟过程中为谷胱甘肽（GSH）的产生提供ATP，并且在早期发育过程中还参与NADPH和GSH的再生。最后，许多病理状况或环境损伤通过改变线粒体功能损害早期发育，这说明了线粒体功能在胚胎发育中的核心地位。
