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Metabolomics of Human Amniotic Fluid and Maternal Plasma during Normal Pregnancy.

ABSTRACT: Metabolic profiles of amniotic fluid and maternal blood are sources of valuable information about fetus development and can be potentially useful in diagnosis of pregnancy disorders. In this study, we applied 1H NMR-based metabolic profiling to track metabolic changes occurring in amniotic fluid (AF) and plasma (PL) of healthy mothers over the course of pregnancy. AF and PL samples were collected in the 2nd (T2) and 3rd (T3) trimester, prolonged pregnancy (PP) until time of delivery (TD). A multivariate data analysis of both biofluids reviled a metabolic switch-like transition between 2nd and 3rd trimester, which was followed by metabolic stabilization throughout the rest of pregnancy probably reflecting the stabilization of fetal maturation and development. The differences were further tested using univariate statistics at ? = 0.001. In plasma the progression from T2 to T3 was related to increasing levels of glycerol, choline and ketone bodies (3-hydroxybutyrate and acetoacetate) while pyruvate concentration was significantly decreased. In amniotic fluid, T2 to T3 transition was associated with decreasing levels of glucose, carnitine, amino acids (valine, leucine, isoleucine, alanine, methionine, tyrosine, and phenylalanine) and increasing levels of creatinine, succinate, pyruvate, choline, N,N-dimethylglycine and urocanate. Lactate to pyruvate ratio was decreased in AF and conversely increased in PL. The results of our study, show that metabolomics profiling can be used to better understand physiological changes of the complex interdependencies of the mother, the placenta and the fetus during pregnancy. In the future, these results might be a useful reference point for analysis of complicated pregnancies.

SUBMITTER: Orczyk-Pawilowicz M

PROVIDER: S-EPMC4829258 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Metabolomics of Human Amniotic Fluid and Maternal Plasma during Normal Pregnancy.

Orczyk-Pawilowicz Magdalena M Jawien Ewa E Deja Stanislaw S Hirnle Lidia L Zabek Adam A Mlynarz Piotr P

PloS one 20160412 4

Metabolic profiles of amniotic fluid and maternal blood are sources of valuable information about fetus development and can be potentially useful in diagnosis of pregnancy disorders. In this study, we applied 1H NMR-based metabolic profiling to track metabolic changes occurring in amniotic fluid (AF) and plasma (PL) of healthy mothers over the course of pregnancy. AF and PL samples were collected in the 2nd (T2) and 3rd (T3) trimester, prolonged pregnancy (PP) until time of delivery (TD). A mult ...[more]

PMID: 27070784

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Project description:BackgroundThe amniotic fluid (AF) cell-free transcriptome is modulated by physiologic and pathologic processes during pregnancy. AF gene expression changes with advancing gestation reflect fetal development and organ maturation; yet, defining normal expression and splicing patterns for biomarker discovery in obstetrics requires larger heterogeneous cohorts, evaluation of potential confounding factors, and novel analytical approaches.MethodsWomen with a normal pregnancy who had an AF sample collected during midtrimester (n?=?30) or at term gestation (n?=?68) were included. Expression profiling at exon level resolution was performed using Human Transcriptome Arrays. Differential expression was based on moderated t-test adjusted p?<?0.05 and fold change >?1.25; for differential splicing, a splicing index >?2 and adjusted p?<?0.05 were required. Functional profiling was used to interpret differentially expressed or spliced genes. The expression of tissue-specific and cell-type specific signatures defined by single-cell genomics was quantified and correlated with covariates. In-silico validation studies were performed using publicly available datasets.Results1) 64,071 genes were detected in AF, with 11% of the coding and 6% of the non-coding genes being differentially expressed between midtrimester and term gestation. Expression changes were highly correlated with those previously reported (R?>?0.79, p?<?0.001) and featured increased expression of genes specific to the trachea, salivary glands, and lung and decreased expression of genes specific to the cardiac myocytes, uterus, and fetal liver, among others. 2) Single-cell RNA-seq signatures of the cytotrophoblast, Hofbauer cells, erythrocytes, monocytes, T and B cells, among others, showed complex patterns of modulation with gestation (adjusted p?<?0.05). 3) In 17% of the genes detected, we found differential splicing with advancing gestation in genes related to brain development processes and immunity pathways, including some that were missed based on differential expression analysis alone.ConclusionsThis represents the largest AF transcriptomics study in normal pregnancy, reporting for the first time that single-cell genomic signatures can be tracked in the AF and display complex patterns of expression during gestation. We also demonstrate a role for alternative splicing in tissue-identity acquisition, organ development, and immune processes. The results herein may have implications for the development of fetal testing to assess placental function and fetal organ maturity.

Project description:The cell-free transcriptome in amniotic fluid (AF) has been shown to be informative of physiologic and pathologic processes in pregnancy; however, the change in AF proteome with gestational age has mostly been studied by targeted approaches. The objective of this study was to describe the gestational age-dependent changes in the AF proteome during normal pregnancy by using an omics platform. The abundance of 1310 proteins was measured on a high-throughput aptamer-based proteomics platform in AF samples collected from women during midtrimester (16-24 weeks of gestation, n = 15) and at term without labor (37-42 weeks of gestation, n = 13). Only pregnancies without obstetrical complications were included in the study. Almost 25% (320) of AF proteins significantly changed in abundance between the midtrimester and term gestation. Of these, 154 (48.1%) proteins increased, and 166 (51.9%) decreased in abundance at term compared to midtrimester. Tissue-specific signatures of the trachea, salivary glands, brain regions, and immune system were increased while those of the gestational tissues (uterus, placenta, and ovary), cardiac myocytes, and fetal liver were decreased at term compared to midtrimester. The changes in AF protein abundance were correlated with those previously reported in the cell-free AF transcriptome. Intersecting gestational age-modulated AF proteins and their corresponding mRNAs previously reported in the maternal blood identified neutrophil-related protein/mRNA pairs that were modulated in the same direction. The first study to utilize an aptamer-based assay to profile the AF proteome modulation with gestational age, it reveals that almost one-quarter of the proteins are modulated as gestation advances, which is more than twice the fraction of altered plasma proteins (~ 10%). The results reported herein have implications for future studies focused on discovering biomarkers to predict, monitor, and diagnose obstetrical diseases.

Project description:The analysis of cerebrospinal fluid (CSF) is used in biomarker discovery studies for various neurodegenerative central nervous system (CNS) disorders. However, little is known about variation of CSF proteins and metabolites between patients without neurological disorders. A baseline for a large number of CSF compounds appears to be lacking. To analyze the variation in CSF protein and metabolite abundances in a number of well-defined individual samples of patients undergoing routine, non-neurological surgical procedures, we determined the variation of various proteins and metabolites by multiple analytical platforms. A total of 126 common proteins were assessed for biological variations between individuals by ESI-Orbitrap. A large spread in inter-individual variation was observed (relative standard deviations [RSDs] ranged from 18 to 148%) for proteins with both high abundance and low abundance. Technical variation was between 15 and 30% for all 126 proteins. Metabolomics analysis was performed by means of GC-MS and nuclear magnetic resonance (NMR) imaging and amino acids were specifically analyzed by LC-MS/MS, resulting in the detection of more than 100 metabolites. The variation in the metabolome appears to be much more limited compared with the proteome: the observed RSDs ranged from 12 to 70%. Technical variation was less than 20% for almost all metabolites. Consequently, an understanding of the biological variation of proteins and metabolites in CSF of neurologically normal individuals appears to be essential for reliable interpretation of biomarker discovery studies for CNS disorders because such results may be influenced by natural inter-individual variations. Therefore, proteins and metabolites with high variation between individuals ought to be assessed with caution as candidate biomarkers because at least part of the difference observed between the diseased individuals and the controls will not be caused by the disease, but rather by the natural biological variation between individuals.

Dataset Information

Metabolomics of Human Amniotic Fluid and Maternal Plasma during Normal Pregnancy.

Publications

Metabolomics of Human Amniotic Fluid and Maternal Plasma during Normal Pregnancy.

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