title: N-carbamylglutamate enhances pregnancy outcome in rats through activation of the PI3K/PKB/mTOR signaling pathway.
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, 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.
authors: State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, China.
authors: Xiangfang
authors: X
authors: Zeng
authors: Zhimin
authors: Z
authors: Huang
authors: Xiangbing
authors: X
authors: Mao
authors: Junjun
authors: J
authors: Wang
authors: Guoyao
authors: G
authors: Wu
authors: Shiyan
authors: S
authors: Qiao
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D019587:Dietary Supplements; D010064:Embryo Implantation / Q000187:drug effects*; D005260:Female; D005971:Glutamates / Q000494:pharmacology*; D053605:Leukemia Inhibitory Factor / Q000096:biosynthesis; D050498:Live Birth; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011247:Pregnancy / Q000187:drug effects / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism
chemical_list: D005971:Glutamates; D053605:Leukemia Inhibitory Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D050796:STAT3 Transcription Factor; D058570:TOR Serine-Threonine Kinases; C494088:Stat3 protein, rat; C006895:N-carbamylglutamate; C546845:mTOR protein, rat; C526901:Rps6kb1 protein, rat