n-carbamylglutamate enhances pregnancy outcome in rats through activation of the pi3kpkbmtor signaling pathwayn-carbamylglutamate提高怀孕的结果在老鼠pi3kpkbmtor信号通路的激活.pdfVIP

N-Carbamylglutamate Enhances Pregnancy Outcome in Rats through Activation of the PI3K/PKB/mTOR Signaling Pathway 1 1 1 1 1,2 1 Xiangfang Zeng , Zhimin Huang , Xiangbing Mao , Junjun Wang , Guoyao Wu , Shiyan Qiao * 1 State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, China, 2 Departments of Animal Science and of Veterinary Integrative Biosciences, Texas AM University, College Station, Texas, United States of America Abstract 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, t