Amino acid signaling for embryonic and fetal development

Tuesday, July 22, 2014: 9:35 AM
2504 (Kansas City Convention Center)
Guoyao Wu , Texas A&M University, College Station, TX
Fuller Bazer , Texas A&M University, College Station, TX
Robert Burghardt , Texas A&M University, College Station, TX
Gregory Johnson , Texas A&M University, College Station, TX
M. Carey Satterfield , Texas A&M University, College Station, TX
Xiaoqiu Wang , Texas A&M University, College Station, TX
Abstract Text:

Embryonic death losses in mammals are estimated to range from 20% to 50% depending on species, with two-thirds of the losses occurring during the peri-implantation period of pregnancy. Additionally, intrauterine growth restriction (IUGR) is primarily responsible for the high rates (up to 15%) of neonatal mortality in livestock species. Among litter-bearing species, swine exhibit the most severe naturally-occurring embryonic loss and IUGR. Nutrient availability, limited uterine capacity, and placental insufficiency are major factors contributing to suboptimal reproduction in mammals.  Emerging evidence also shows that concentrations of several amino acids (arginine, glutamine and leucine) in the uterine lumen increase markedly during early pregnancy and are particularly abundant in fetal allantoic fluid during early and mid-gestation. Besides serving as building blocks for proteins, these amino acids play signaling roles to regulate intracellular protein turnover, water and ion transport, apoptosis, immune responses, and anti-oxidative reactions in the conceptus (embryo/fetus and extra-embryonic membranes).  Specifically, arginine is the precursor for synthesis of nitric oxide and polyamines (putrescine, spermidine, and spermine) that are essential to DNA synthesis and cell proliferation.  Interestingly, these synthetic pathways are regulated by physiological concentrations of glutamine and leucine to coordinate the cellular actions of arginine.  In addition, glutamine and leucine increase expression and activity of glutamine:fructose-6-phosphate transaminase to stimulate formation of glucosamine-6-phosphate from glutamine and fructose-6-phosphate and, therefore, for active synthesis of amino sugars and glycoproteins by trophectoderm cells. Furthermore, arginine, glutamine, and leucine activate: (1) the mechanistic target of rapamycin (MTOR) cell signaling through phosphorylation of the MTOR protein and its downstream target proteins (S6K1 and 4E-BP1); and (2) osteopontin-induced cell signaling (a major mechanism for regulation of cell adhesion and implantation) through binding αvβ3 and α5β1 integrin heterodimers and the subsequent phosphorylation of MAPK3/MAPK1 (Erk1/2) and MAPK14 (p38).  The beneficial outcome is to promote conceptus growth and development. Arginine and osteopontin appear to activate sequentially PI3K, Akt1, and MTOR to amplify cell signal transduction and exert their physiological effects. Translating the basic research into feeding practices, i.e., supplementing 0.4% or 0.8% arginine to a typical corn- and soybean meal-based diet (containing 0.7% arginine) for gilts between d 14 and 25 of gestation, increases embryonic survival and conceptus development. As profitability of the swine industry critically depends on reproductive efficiency of sows, our findings have important implications for increasing pork production to provide high-quality animal protein for human consumption.

Keywords: pig, nutrition and biochemistry