Pregnancy-Induced Metabolic Phenotype Variations in Maternal Plasma

Abstract

Metabolic variations occur during normal pregnancy to provide the growing fetus with a supply of nutrients required for its development and to ensure the health of the woman during gestation. Mass spectrometry-based metabolomics was employed to study the metabolic phenotype variations in the maternal plasma that are induced by pregnancy in each of its three trimesters. Nontargeted metabolomics analysis showed that pregnancy significantly altered the profile of metabolites in maternal plasma. The levels of six metabolites were found to change significantly throughout pregnancy, with related metabolic pathway variations observed in biopterin metabolism, phospholipid metabolism, amino acid derivatives, and fatty acid oxidation. In particular, there was a pronounced elevation of dihydrobiopterin (BH₂), a compound produced in the synthesis of dopa, dopamine, norepinephrine, and epinephrine, in the second trimester, whereas it was markedly decreased in the third trimester. The turnover of BH₂ and tryptophan catabolites indicated that the fluctuations of neurotransmitters throughout pregnancy might reveal the metabolic adaption in the maternal body for the growth of the fetus. Furthermore, 11 lipid classes and 41 carnitine species were also determined and this showed variations in the presence of long-chain acylcarnitines and lysophospholipids in later pregnancy, suggesting changes of acylcarnitines and lysophospholipids to meet the energy demands in pregnant women. To our knowledge, this work is the first report of dynamic metabolic signatures and proposed related metabolic pathways in the maternal plasma for normal pregnancies and provided the basis for time-dependent metabolic trajectory against which disease-related disorders may be contrasted.

Multiple Micronutrient Needs in Pregnancy in Industrialized Countries

“…This leads to increased stores during the first trimester, followed by enhanced release and increased levels of circulating nutrients in the last part of pregnancy, corresponding to exponential fetal growth. A recent trial analyzed the metabolic phenotype variations in maternal plasma of 180 healthy pregnant women, using a metabolomics approach in the three trimesters [12]. Nontargeted metabolic profiling analysis showed a profound alteration in the macronutrient metabolic phenotype with a statistically significant separation between trimesters mainly due to amino acid and lipid metabolism [12].…”

“…A recent trial analyzed the metabolic phenotype variations in maternal plasma of 180 healthy pregnant women, using a metabolomics approach in the three trimesters [12]. Nontargeted metabolic profiling analysis showed a profound alteration in the macronutrient metabolic phenotype with a statistically significant separation between trimesters mainly due to amino acid and lipid metabolism [12]. These metabolic changes are demonstrable even for micronutrients.…”

1H NMR-based metabolomics study on the physiological variations during the rat pregnancy process

“…Substantially, these physiological variations come from the metabolic changes during the pregnant period (King, 2000;Luan et al, 2014), which are complex and widespread, resulting in the maternal metabolism working from a different baseline compared with the non-pregnant state. Among the reported changes, those in amino acid metabolism, energy and gut microflora metabolisms were observed in connection to pregnancy (Pinto et al, 2015).…”

“…In addition, carbohydrate metabolism received particular concerns due to the wellrecognized clinical disorder known as diabetes mellitus (Hernandez et al, 2014). Recently, an untargeted metabolomics analysis with LC-MS and shotgun lipidomics of maternal plasma showed that the levels of dihydrobiopterin (BH 2 ), carnitine, acetylalanine, leucyl-phenylalanine, lysophosphatidylcholine (LPC) (18:1), and LPC (20:4), were found to change significantly throughout pregnancy, as well as the changes in the total concentrations of LPCs, phosphatidylcholines (PHCs), lysophosphatidylethanolamines (LPEs) and lysophosphatidylserines (LPSs) (Luan et al, 2014). Meanwhile, the dynamic metabolic adaptations of maternal urine from healthy pregnancies has been evaluated by NMR-based metabolomics techniques, in which the levels of 21 metabolites including choline, creatinine, 4-deoxyerythronic acid, 4-deoxythreonic acid, furoylglycine, guanidoacetate, 3-hydroxybutyrate, and lactate were found to change significantly throughout pregnancy (Diaz et al, 2013).…”

Quality control-based signal drift correction and interpretations of metabolomics/proteomics data using random forest regression

“…Based on a controlled experiment involved QC samples throughout the data collection process, the most advantageous uses of QC samples can be obtained, allowing the correction of signal drift and other systematic noise through mathematical algorithms in liquid or gas chromatography (LC or GC) hyphenated to MS-based metabolomics study 5,6 . However, there is few such controlled experiment and algorithms for improving the data quality in label-free LC-MS based proteomics 4,7 .…”