¹H NMR Based Metabonomics of Human Amniotic Fluid for the Metabolic Characterization of Fetus Malformations

Abstract

An NMR-metabonomic study of malformed fetuses was carried out through human amniotic fluid (HAF) analysis. Over 70 compounds were detected in control HAF by NMR. Possible confounding variables (fetus gender and gestational and maternal ages) were shown not to induce detectable compositional trends in the control group considered. Malformed fetuses showed variations in glucose, some amino acids and organic acids and proteins. In tandem with enzymatic assays, these NMR results suggest that changes in gycolysis and gluconeogenesis as well as kidney underdevelopment occur in the malformed fetuses studied here.

Impact of prenatal stress on 1H NMR-based metabolic profiling of rat amniotic fluid

“…The metabolic variations observed on the NMR profile of amniotic fluid are related to the gluconeogenic amino acid pathway; alanine, glutamate, glutamine, isoleucine, valine, tyrosine and phenylalanine were lower in the hyperthermic than in the control group. A recent study [2] described a decrease in the gluconeogenic amino acids in human amniotic fluid in foetus malformation, probably due to increased glucose production via gluconeogenesis which is active around 16 weeks of gestation in the developing liver. This may be consistent with the need to replenish the glucose levels available to other tissues following hypoxia, compensating for the lack of foetal blood oxygenation described by Regnault et al [48].…”

“…Biochemical assays only target a few predefined metabolites for analysis. Using 1 H NMR spectroscopy metabonomic approaches, over 70 compounds can be targeted [2,3]. This technique, which has been used to elucidate both endogenous and drug-related metabolites, has proved an effective method for monitoring disease states and has been used to study the metabolism and toxicity of pharmacologically active agents [4].…”

“…However, there is increasing research on pregnancy focussing on metabolomics, including studies based on maternal serum/plasma [8,9], embryonic culture medium [10,11], amniotic fluid [2,12,13], oocytes [14,15] and placental tissue [16,17].The composition of amniotic fluid reflects both the mother's health and foetal status and development [2]. Previous NMR studies have shown a correlation between human amniotic fluid composition and disorders such as open spinabifida [18,19] and diabetes mellitus [20], as well as foetal lung [21] and kidney [18] maturation and normative metabolite concentration during gestation [22].…”

Radiation-Induced Metabolomic Changes in Sterile Male Μοnochamus alternatus (Coleoptera: Cerambycidae)

“…It separates the systematic variation in X (process variables) into two parts, one that is linearly related to Y (response variables) and one that is orthogonal to Y . This may lead to better class resolution in a discriminant problem, and give a more straight forward and realistic model ( Kuhl et al 2008 , Wiklund et al 2008 , Graca et al 2009 , Wu et al 2012 ). In OPLS-DA model, R 2 X (cum) is the percentage of cumulative variation of the data explained by the mode and represents the goodness of the fit to the model.…”

Impact of fetal chromosomal disorders on maternal blood metabolome: toward new biomarkers?

“…11, [16][17][18][19][20][21][22][23] Understanding of the impact of prenatal disorders on fetal/maternal metabolisms has been sought regarding preeclampsia, 7,16,17,20,21 fetal malformations, 1,2,11,14,24,25 preterm delivery, 3,5,9,14,21,26 gestational diabetes mellitus, 5,11,12,14 small for gestational age 6,8,10 and fetal chromosomal disorders (CD). 2,11,14,15,18,19,21,27 The underlying challenges have been two-fold, either searching for predictive biomarkers of conditions such as preeclampsia or preterm, or seeking disease metabolic descriptions to complement existing clinical strategies.…”