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.
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ABSTRACT: The present review focuses on the physiological functions of glutamate-glutamine exchange involving placental amino acid transport and umbilical amino acid uptake in mammals (particularly in sows), with special emphasis on the associated regulating mechanisms. Glutamate plus glutamine are among the most abundant and the most utilized amino acids in fetus during late gestation. During pregnancy, amino acids, notably as precursors of macromolecules including proteins and nucleotides are involved in fetal development and growth. Amino acid concentrations in fetus are generally higher than in the mother. Among amino acids, the transport and metabolism of glutamate and glutamine during fetal development exhibit characteristics that clearly emphasize the importance of the interaction between the placenta and the fetal liver. Glutamate is quite remarkable among amino acids, which originate from the placenta, and is cleared from fetal plasma. In addition, the flux of glutamate through the placenta from the fetal plasma is highly correlated with the umbilical glutamate delivery rate. Glutamine plays a central role in fetal carbon and nitrogen metabolism and exhibits one of the highest fetal/maternal plasma ratio among all amino acids in human and other mammals. Glutamate is taken up by placenta from the fetal circulation and then converted to glutamine before being released back into the fetal circulation. Works are required on the glutamate-glutamine metabolism during late pregnancy in physiological and pathophysiological situations since such works may help to improve fetal growth and development both in humans and other mammals. Indeed, glutamine supplementation appears to ameliorate fetal growth retardation in sows and reduces preweaning mortality of piglets.Amino Acids 11/2014; DOI:10.1007/s00726-014-1861-5 · 3.65 Impact Factor
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ABSTRACT: As the interface between the mother and the developing fetus, the placenta is believed to play an important role in assisted reproductive technology (ART)-induced aberrant intrauterine and postnatal development. However, the mechanisms underlying aberrant placentation remain unclear, especially during the extra-embryonic tissue development and early stage of placental formation. Using a mouse model, this investigation provides the first comparative proteomic analysis of in vivo (IVO) and in vitro produced (IVP) extra-embryonic tissues and placentas after in vivo fertilization and development, or in vitro fertilization and culture, respectively. We identified 165 and 178 differentially expressed proteins (DEPs) between IVO and IVP extra-embryonic tissues and placentas on Embryonic Day 7.5 (E7.5) and E10.5, respectively. Many DEPs were functionally associated with genetic information processing, such as impaired de novo DNA methylation, as well as post-transcriptional, translational and post-translational dysregulation. These novel findings were further confirmed by global hypomethylation, and a lower level of correlation was found between the transcriptome and proteome in the IVP groups. In addition, numerous DEPs were involved in energy and amino acid metabolism, cytoskeleton organization and transport, and vasculogenesis and angiogenesis. These disturbed processes and pathways are likely to be associated with embryonic intrauterine growth restriction, an enlarged placenta and impaired labyrinth morphogenesis. This study provides a direct and comprehensive reference for the further exploration of the placental mechanisms that underlie ART-induced developmental aberrations.Biology of Reproduction 10/2014; DOI:10.1095/biolreprod.114.124248 · 3.45 Impact Factor
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ABSTRACT: Abstract (1)H-NMR spectroscopy coupled with multivariate statistical analysis was used for the first time to compare the urinary NMR metabolic profiles of neonates with intrauterine growth retardation (IUGR) and large for gestational age (LGA). For the sake of comparison, infants who were adequate for gestational age (AGA) were also analyzed. Pattern recognition methods, including Principal Component Analyses (PCA), Partial Least Squares Discriminant Analysis (PLS-DA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), were used to analyze NMR data. Clear differences among the metabolic profiles of AGA, IUGR and LGA were observed. The main metabolites responsible for these differentiations were identified as myo-inositol, creatinine, creatine, citrate, urea and glycine. In particular, among these, myo-inositol may be a potential biomarker of an altered glucose metabolism during fetal development both in IUGR and LGA. This study highlights the applicability of NMR-based metabolomics for improving the understanding of the relations among nutrition, integrated metabolism and health in neonatology.Journal of Maternal-Fetal and Neonatal Medicine 10/2014; 27 Suppl 2:13-9. DOI:10.3109/14767058.2014.955674 · 1.21 Impact Factor