Role of glucose in cloned mouse embryo development
Role of glucose in cloned mouse embryo development
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DOI：
10.1152/ajpendo.00683.2007
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发表时间：
2008-10-01
影响因子：
5.1
通讯作者：
Latham, Keith E.
中科院分区：
文献类型：
--
作者：
Han, Zhiming;Vassena, Rita;Latham, Keith E.
克隆的小鼠胚胎对含葡萄糖的培养液表现出明显的偏好，在含葡萄糖的培养液中促进了囊胚期的发育，这主要归因于在第一个细胞周期中的早期有益作用。葡萄糖的这种早期有益作用在孤雌生殖、受精或四倍体核移植对照胚胎中没有表现出来，表明它是二倍体克隆所特有的。在克隆胚胎中，也可以看到葡萄糖转运蛋白SLC2A1在细胞表面的早熟定位，以及葡萄糖转运蛋白表达的增加和单细胞和双细胞阶段葡萄糖摄取的增加。为了研究葡萄糖在早期克隆胚胎发育中的作用，我们检测了葡萄糖代谢和相关代谢物，以及线粒体的超微结构、分布和数量。与孤雌生殖对照相比，用卵丘细胞核制备的克隆在2-细胞期的葡萄糖代谢显著增强。尽管新陈代谢增加，但与单性生殖和受精对照相比，无性系的ATP含量降低。与孤雌生殖对照相比，这两个阶段的克隆都表现出更高的糖原浓度。线粒体数量无明显变化，但克隆线粒体出现超微结构改变。有趣的是，葡萄糖的供应对线粒体的结构和定位有积极的影响。我们得出结论，克隆胚胎在最初的两个细胞周期中可能会在依赖ATP的过程中受到严重损害，并且葡萄糖可能通过对线粒体的积极作用来发挥其早期的有益作用。
Cloned mouse embryos display a marked preference for glucose-containing culture medium, with enhanced development to the blastocyst stage in glucose-containing medium attributable mainly to an early beneficial effect during the first cell cycle. This early beneficial effect of glucose is not displayed by parthenogenetic, fertilized, or tetraploid nuclear transfer control embryos, indicating that it is specific to diploid clones. Precocious localization of the glucose transporter SLC2A1 to the cell surface, as well as increased expression of glucose transporters and increased uptake of glucose at the one- and two-cell stages, is also seen in cloned embryos. To examine the role of glucose in early cloned embryo development, we examined glucose metabolism and associated metabolites, as well as mitochondrial ultrastructure, distribution, and number. Clones prepared with cumulus cell nuclei displayed significantly enhanced glucose metabolism at the two-cell stage relative to parthenogenetic controls. Despite the increase in metabolism, ATP content was reduced in clones relative to parthenotes and fertilized controls. Clones at both stages displayed elevated concentrations of glycogen compared with parthenogenetic controls. There was no difference in the number of mitochondria, but clone mitochondria displayed ultrastructural alterations. Interestingly, glucose availability positively affected mitochondrial structure and localization. We conclude that cloned embryos may be severely compromised in terms of ATP-dependent processes during the first two cell cycles and that glucose may exert its early beneficial effects via positive effects on the mitochondria.