Johnson Gregory A, Seo Heewon, Bazer Fuller W, Wu Guoyao, Kramer Avery C, McLendon Bryan A, Cain Joe W
Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas, USA.
Department of Animal Science, Texas A&M University, College Station, Texas, USA.
Mol Reprod Dev. 2023 Jul;90(7):673-683. doi: 10.1002/mrd.23570. Epub 2022 Apr 22.
Conceptus elongation and early placentation involve growth and remodeling that requires proliferation and migration of cells. This demands conceptuses expend energy before establishment of a placenta connection and when they are dependent upon components of histotroph secreted or transported into the uterine lumen from the uterus. Glucose and fructose, as well as many amino acids (including arginine, aspartate, glutamine, glutamate, glycine, methionine, and serine), increase in the uterine lumen during the peri-implantation period. Glucose and fructose enter cells via their transporters, SLC2A, SLC2A3, and SLC2A8, and amino acids enter the cells via specific transporters that are expressed by the conceptus trophectoderm. However, porcine conceptuses develop rapidly through extensive cellular proliferation and migration as they elongate and attach to the uterine wall resulting in increased metabolic demands. Therefore, coordination of multiple metabolic biosynthetic pathways is an essential aspect of conceptus development. Oxidative metabolism primarily occurs through the tricarboxylic acid (TCA) cycle and the electron transport chain, but proliferating and migrating cells, like the trophectoderm of pigs, enhance aerobic glycolysis. The glycolytic intermediates from glucose can then be shunted into the pentose phosphate pathway and one-carbon metabolism for the de novo synthesis of nucleotides. A result of aerobic glycolysis is limited availability of pyruvate for maintaining the TCA cycle, and trophectoderm cells likely replenish TCA cycle metabolites primarily through glutaminolysis to convert glutamine into TCA cycle intermediates. The synthesis of ATP, nucleotides, amino acids, and fatty acids through these biosynthetic pathways is essential to support elongation, migration, hormone synthesis, implantation, and early placental development of conceptuses.
胚胎伸长和早期胎盘形成涉及生长和重塑，这需要细胞增殖和迁移。这要求胚胎在建立胎盘连接之前以及依赖从子宫分泌或转运到子宫腔的组织营养成分时消耗能量。在着床期，子宫腔内的葡萄糖、果糖以及许多氨基酸（包括精氨酸、天冬氨酸、谷氨酰胺、谷氨酸、甘氨酸、蛋氨酸和丝氨酸）会增加。葡萄糖和果糖通过其转运蛋白SLC2A、SLC2A3和SLC2A8进入细胞，氨基酸则通过胚胎滋养外胚层表达的特定转运蛋白进入细胞。然而，猪胚胎在伸长并附着于子宫壁时，通过广泛的细胞增殖和迁移迅速发育，导致代谢需求增加。因此，多种代谢生物合成途径的协调是胚胎发育的一个重要方面。氧化代谢主要通过三羧酸（TCA）循环和电子传递链进行，但像猪的滋养外胚层这样的增殖和迁移细胞会增强有氧糖酵解。来自葡萄糖的糖酵解中间产物随后可被分流到磷酸戊糖途径和一碳代谢中，用于核苷酸的从头合成。有氧糖酵解的一个结果是丙酮酸用于维持TCA循环的可用性有限，滋养外胚层细胞可能主要通过谷氨酰胺分解将谷氨酰胺转化为TCA循环中间产物来补充TCA循环代谢物。通过这些生物合成途径合成ATP、核苷酸、氨基酸和脂肪酸对于支持胚胎的伸长、迁移、激素合成、着床和早期胎盘发育至关重要。
