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: Ray Kruse Iles[Show abstract] [Hide abstract]
ABSTRACT: In this data-rich age it is no longer necessary to methodically isolate, characterize and measure specific molecules. What is important is to identify which of the hundreds or thousands of resolved and measured 'unknown' molecules are potentially associated with the pathophysiology of interest. We have taken LC-MS data from pregnancy urine and applied SIMCA P+ data analysis software in shotgun metabolomics to search the large amount of data for significant metabolite changes that occur in the transition from the first to early second trimester of pregnancy. Seventy-two individual urine samples were examined spanning 9-23 weeks of gestation. Three-hundred and eighty-three ions were identified and variations were mapped between profiles of different gestational age and the significance quantified. In urine collected during pregnancy, the transition from first to early second trimester revealed a relatively steady pattern of metabolites except for four that showed a dramatic fall in abundance as pregnancy progressed from the first to second trimester. The pattern of changes in urinary metabolites identified by Zwitterionic Hydrophilic Liquid Interaction Chromatography (ZIC-HILIC) coupled to mass spectrometry was evaluated and we established a baseline of changes from which a search for metabolomic markers associated with clinical pathologies of pregnancy can be made as a part of wider ultraomics study. Copyright © 2014 John Wiley & Sons, Ltd.Biomedical Chromatography 06/2014; · 1.95 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Gestational diabetes mellitus, intrauterine growth restriction and pre-eclamptic toxaemia are common pregnancy complications that can have detrimental effects on morbidity and mortality of mother and fetus as well as long term health outcomes. Although they are distinct conditions, they may occur together and are often considered together as they share a common aetiology of inadequate placental perfusion. The discovery and study of preventative treatments is hampered by a lack of effective screening tools to accurately identify women at the highest risk of disease. Metabolomics, an omic science, is the global quantitative assessment of endogenous metabolites within a biological system. It has proven to be a rapid approach in the identification of biomarkers predictive of the outcome of a pathological condition and the individual's response to a pharmacological treatment. We review the current and potential applications of metabolomics in maternal-fetal medicine, focusing on its use as a biomarker for great obstetrical syndromes diagnosis.Bailliè re s Best Practice and Research in Clinical Obstetrics and Gynaecology 08/2014; · 2.02 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: L-Glutamine (Gln) is an essential amino acid for intestinal growth and integrity. However, the underlying molecular mechanisms are not fully known. In the present study, porcine intestinal epithelial cells (IPEC-1) were used to test the hypothesis that autophagy is induced by Gln deprivation and inhibited by Gln supplementation. After a 2-day period of growth in normal medium, IPEC-1 cells were transferred to a Gln-free custom-made DMEM. Cell numbers, the distribution of autophagosomes, the abundance of the protein for an autophagy marker LC3B, as well as abundances of the mTOR and MAPK proteins during an 8-h period were determined. Furthermore, the rescue effect of 5 mM Gln was evaluated. Our results showed that Gln deprivation reduced the cell number, while enhancing the accumulation of autophagosomes and the expression of LC3B-II in IPEC-1 cells within 8 h. The concentrations of Glu, Asp, Cit, Arg, Leu, Ile, Val, Ala, β-Ala, Orn, Phe, Met and Ser in the culture medium were altered by Gln deprivation. Further analysis revealed that Gln deficiency inactivated, but Gln supplementation activated, the mTOR and MAPK/ERK signaling pathways. Collectively, our findings support the notion that Gln deficiency induces autophagy and disturbs amino acid metabolism in intestinal epithelial cells, as well as attenuated their mTOR and MAPK/ERK signaling pathways to inhibit protein synthesis and cell proliferation.Amino Acids 07/2014; · 3.91 Impact Factor