Metabolomic Analysis Reveals Differences in Umbilical Vein Plasma Metabolites between Normal and Growth-Restricted Fetal Pigs during Late Gestation
ABSTRACT Intrauterine growth restriction (IUGR) remains a major problem for both human health and animal production due to its association with high rates of neonatal morbidity and mortality, low efficiency of food utilization, permanent adverse effects on postnatal growth and development, and long-term health and productivity of the offspring. However, the underlying mechanisms for IUGR are largely unknown. In this study, one IUGR fetus and one normal body weight (NBW) fetus were obtained from each of 9 gilts at each of 2 gestational ages (d 90 and 110). Metabolomes of umbilical vein plasma in IUGR and NBW fetuses were determined by MS, while hormones, amino acids, and related metabolites in maternal and fetal plasma were measured using assay kits and chromatographic methods. Metabolites (including glucose, urea, ammonia, amino acids, and lipids) in umbilical vein plasma exhibited a cluster of differences between IUGR and NBW fetuses on d 90 and 110 of gestation. These changes in the IUGR group are associated with disorders of nutrient and energy metabolism as well as endocrine imbalances, which may contribute to the retardation of fetal growth and development. The findings help provide information regarding potential mechanisms responsible for IUGR in swine and also have important implications for the design of effective strategies to prevent, diagnose, and treat IUGR in other mammalian species, including humans.
- SourceAvailable from: Xiaoqiu Wang
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- "On the basis of utilization of amino acids for protein synthesis, the maternal supply of amino acids differs both quantitatively and qualitatively with advancing gestation. Arginine, containing four nitrogen atoms per molecule, is the most abundant nitrogen carrier in fetus, while glutamine is the most abundant nitrogen supplier in porcine umbilical vein during late gestation (Table 1) (Lin et al. 2012). Thus, the rate of fetal glutamine accretion is the greatest throughout the gestation in pigs (Wu et al. 1999). "
ABSTRACT: Intrauterine growth restriction (IUGR) is one of the most common concerns in human obstetrics and domestic animal production. It is usually caused by placental insufficiency, which decreases fetal uptake of nutrients (especially amino acids) from the placenta. Amino acids are not only building blocks for protein but also key regulators of metabolic pathways in fetoplacental development. The enhanced demands of amino acids by the developing conceptus must be met via active transport systems across the placenta as normal pregnancy advances. Growing evidence indicates that IUGR is associated with a reduction in placental amino acid transport capacity and metabolic pathways within the embryonic/fetal development. The positive relationships between amino acid concentrations in circulating maternal blood and placental amino acid transport into fetus encourage designing new therapies to prevent or treat IUGR by enhancing amino acid availability in maternal diets or maternal circulation. Despite the positive effects of available dietary interventions, nutritional therapy for IUGR is still in its infancy. Based on understanding of the underlying mechanisms whereby amino acids promote fetal growth and of their dietary requirements by IUGR, supplementation with functional amino acids (e.g., arginine and glutamine) hold great promise for preventing fetal growth restriction and improving health and growth of IUGR offspring.Amino Acids 03/2014; 46. DOI:10.1007/s00726-014-1725-z · 3.65 Impact Factor
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ABSTRACT: Rising evidence points towards the critical and long-term involvement of prenatal and early nutrition and lifestyle on later health and disease risk predisposition. Metabolomics is now a well established top-down system biology approach that explores genetic-environment-health paradigm. The generalization of such approaches has opened new research areas to deepen our current understanding on many physiological processes as well as foods and nutrient functionalities in target populations. It is envisioned that this will provide new avenues towards preventive medicine and prognostic strategies for tailored therapeutic and personalized nutrition management. The development of system biology approaches and the new generation of biomarker patterns will provide the opportunity to associate complex metabolic regulations to the etiology of multifactorial pediatric diseases. This may subsequently lead to the development of system mechanistic hypotheses that could be targeted with new nutritional personalized concepts. Therefore, this review aims at describing recent applications of metabolomics in pre-clinical and clinical fields with insights into disease diagnostics/monitoring and improvement of homeostasis metabolic regulation which may be translatable to novel therapeutic and nutrition advances in pediatric research.Pediatric Research (2013); doi:10.1038/pr.2013.1.Pediatric Research 01/2013; 73(4). DOI:10.1038/pr.2013.1 · 2.84 Impact Factor
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ABSTRACT: PURPOSE OF REVIEW: Intrauterine growth restriction (IUGR) occurs when fetal growth rate falls below the genetic potential and affects a significant number of pregnancies, but still no therapy has been developed for this pregnancy disease. This article reviews the most recent findings concerning maternal characteristics and behaviours predisposing to IUGR as well as maternal early markers of the disease. A comprehensive understanding of factors associated with IUGR will help in providing important tools for preventing and understanding adverse outcomes. RECENT FINDINGS: Maternal nutritional status, diet and exposure to environmental factors are increasingly acknowledged as potential factors affecting fetal growth both by altering nutrient availability to the fetus and by modulating placental gene expression, thus modifying placental function. SUMMARY: Assessing nutritional and environmental factors associated with IUGR, and the molecular mechanisms by which they may have a role in the disease onset, is necessary to provide comprehensive and common guidelines for maternal care and recommended behaviours. Moreover, maternal genetic predispositions and early serum markers may allow a better and more specific monitoring of high risk pregnancies, optimizing the timing of delivery.02/2013; 16(3). DOI:10.1097/MCO.0b013e32835e8d9c