State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, China.
PLoS One. 2012;7(7):e41192. doi: 10.1371/journal.pone.0041192. Epub 2012 Jul 27.
Administration of N-carbamylglutamate (NCG), an analogue of endogenous N-acetyl-glutamate (an activator of arginine synthesis) has been shown to enhance neonatal growth by increasing circulating arginine levels. However, the effect of NCG on pregnancy remains unknown. This study examined the effects of NCG on pregnancy outcome and evaluated potential mechanisms involved. Reproductive performance, embryo implantation, and concentration of amino acids in serum and uterine flushing, were determined in rats fed control or NCG supplemented diets. Ishikawa cells and JAR cells were used to examine the mechanism by which NCG affects embryo implantation. Dietary NCG supplementation increased serum levels of arginine, onithine, and proline, as well as uterine levels of arginine, glutamine, glutamate, and proline. Additionally, it stimulated LIF expression, and enhanced the activation of signal transduction and activator of transcription 3 (Stat3), protein kinase B (PKB), and 70-kDa ribosomal protein S6 kinase (S6K1) during the periimplantation period, resulting in an increase in litter size but not birth weight. In uterine Ishikawa cells, LIF expression was also enhanced by treatment with arginine and its metabolites. In trophoblast JAR cells, treatment with arginine and its metabolites enhanced Stat3, PKB, and S6K1 activation and facilitated cellular adhesion activity. These effects were abolished by pretreatment with inhibitors of phosphatidylinositol 3-kinase (wortmannin) and mammalian target of rapamycin (rapamycin). The results demonstrate that NCG supplementation enhances pregnancy outcome and have important implications for the pregnancy outcome of mammalian species.
N- 氨甲酰谷氨酸（NCG）是内源性 N- 乙酰谷氨酸（精氨酸合成的激活剂）的类似物，已被证明通过增加循环精氨酸水平来促进新生儿生长。然而，NCG 对妊娠的影响尚不清楚。本研究检查了 NCG 对妊娠结局的影响，并评估了涉及的潜在机制。在给予对照或 NCG 补充饮食的大鼠中，测定了生殖性能、胚胎着床和血清及子宫冲洗中氨基酸的浓度。使用 Ishikawa 细胞和 JAR 细胞研究了 NCG 影响胚胎着床的机制。膳食 NCG 补充增加了血清中精氨酸、鸟氨酸和脯氨酸以及子宫中精氨酸、谷氨酰胺、谷氨酸和脯氨酸的浓度。此外，它刺激了 LIF 表达，并在着床期增强了信号转导和转录激活因子 3（Stat3）、蛋白激酶 B（PKB）和 70-kDa 核糖体蛋白 S6 激酶（S6K1）的激活，导致窝仔数增加，但出生体重没有增加。在子宫 Ishikawa 细胞中，精氨酸及其代谢物处理也增强了 LIF 表达。在滋养层 JAR 细胞中，精氨酸及其代谢物处理增强了 Stat3、PKB 和 S6K1 的激活并促进了细胞黏附活性。这些作用被磷脂酰肌醇 3-激酶（wortmannin）和雷帕霉素（rapamycin）的抑制剂预处理所消除。结果表明，NCG 补充增强了妊娠结局，对哺乳动物的妊娠结局具有重要意义。
