Global metabolomic profiling reveals hepatic biosignatures that reflect the unique metabolic needs of late‐term mother and fetus

Saini, Nipun; Virdee, Manjot S; Helfrich, Kaylee K.; Kwan, Sze Ting Cecilia; Smith, Susan

doi:10.1007/s11306-021-01773-8

Cited by 4 publications

(4 citation statements)

References 60 publications

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“…Thus, fetal metabolic processes are quite distinct from those of its mother, and it must rely on her for those missing processes. We previously reported that, in a normal pregnancy, maternal and fetal hepatic profiles differ significantly [ 31 ]. The fetus has reduced hepatic glucose and essential amino acid pools compared to its mother, and it depends entirely on maternal pools for the same.…”

Section: Discussionmentioning

confidence: 99%

“…The fetus has reduced hepatic glucose and essential amino acid pools compared to its mother, and it depends entirely on maternal pools for the same. Fetal hepatic pools are enriched in serine, glycine, aspartate, and glutamate, which reflects their due contributions to endogenous nucleotide synthesis and protein synthesis [ 31 ]. Finally, with respect to alcohol metabolism, although the mother and fetus experience similar alcohol concentrations [ 36 , 37 , 38 ] the fetal liver has lower abundance of P450 enzymes (approx.…”

Section: Discussionmentioning

confidence: 99%

“…Untargeted metabolite analysis was performed by Metabolon (Durham, NC, USA). The detailed methods used by Metabolon for metabolite separation, detection, and alignment are presented in [ 28 , 31 ] and appended as supplementary methods. Briefly, the protein samples were extracted in methanol and separated using reverse phase/ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS)/MS with positive and negative ion mode electrospray ionization.…”

Section: Methodsmentioning

confidence: 99%

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Untargeted Metabolome Analysis Reveals Reductions in Maternal Hepatic Glucose and Amino Acid Content That Correlate with Fetal Organ Weights in a Mouse Model of Fetal Alcohol Spectrum Disorders

et al. 2022

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Prenatal alcohol exposure (PAE) causes fetal growth restrictions. A major driver of fetal growth deficits is maternal metabolic disruption; this is under-investigated following PAE. Untargeted metabolomics on the dam and fetus exposed to alcohol (ALC) revealed that the hepatic metabolome of ALC and control (CON) dams were distinct, whereas that of ALC and CON fetuses were similar. Alcohol reduced maternal hepatic glucose content and enriched essential amino acid (AA) catabolites, N-acetylated AA products, urea content, and free fatty acids. These alterations suggest an attempt to minimize the glucose gap by increasing gluconeogenesis using AA and glycerol. In contrast, ALC fetuses had unchanged glucose and AA levels, suggesting an adequate draw of maternal nutrients, despite intensified stress on ALC dams. Maternal metabolites including glycolytic intermediates, AA catabolites, urea, and one-carbon-related metabolites correlated with fetal liver and brain weights, whereas lipid metabolites correlated with fetal body weight, indicating they may be drivers of fetal weight outcomes. Together, these data suggest that ALC alters maternal hepatic metabolic activity to limit glucose availability, thereby switching to alternate energy sources to meet the high-energy demands of pregnancy. Their correlation with fetal phenotypic outcomes indicates the influence of maternal metabolism on fetal growth and development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Untargeted Metabolome Analysis Reveals Reductions in Maternal Hepatic Glucose and Amino Acid Content That Correlate with Fetal Organ Weights in a Mouse Model of Fetal Alcohol Spectrum Disorders

et al. 2022

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“…An untargeted metabolite analysis of the bloodspot samples was performed by Metabolon, Inc. (Durham, NC), using a proprietary process as detailed in Saini et al [34]. In summary, samples were analyzed using reverse phase/ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS)/MS with ion mode electrospray ionization (both positive and negative) [35].…”

Section: Metabolomic Analysismentioning

confidence: 99%

Untargeted Metabolome Analysis of Alcohol-Exposed Pregnancies Reveals Metabolite Differences That Are Associated with Infant Birth Outcomes

et al. 2022

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Prenatal alcohol exposure can produce offspring growth deficits and is a leading cause of neurodevelopmental disability. We used untargeted metabolomics to generate mechanistic insight into how alcohol impairs fetal development. In the Western Cape Province of South Africa, 52 women between gestational weeks 5–36 (mean 18.5 ± 6.5) were recruited, and they provided a finger-prick fasting bloodspot that underwent mass spectrometry. Metabolomic data were analyzed using partial least squares-discriminant analyses (PLS-DA) to identify metabolites that correlated with alcohol exposure and infant birth outcomes. Women who consumed alcohol in the past seven days were distinguished by a metabolite profile that included reduced sphingomyelins, cholesterol, and pregnenolones, and elevated fatty acids, acyl and amino acyl carnitines, and androsterones. Using PLS-DA, 25 of the top 30 metabolites differentiating maternal groups were reduced by alcohol with medium-chain free fatty acids and oxidized sugar derivatives having the greatest influence. A separate ortho-PLS-DA analysis identified a common set of 13 metabolites that were associated with infant length, weight, and head circumference. These included monoacylglycerols, glycerol-3-phosphate, and unidentified metabolites, and most of their associations were negative, implying they represent processes having adverse consequences for fetal development.

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A metabolomic study on the effect of prenatal exposure to Benzophenone-3 on spontaneous fetal loss in mice

Han

et al. 2022

Ecotoxicology and Environmental Safety

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Global metabolomic profiling reveals hepatic biosignatures that reflect the unique metabolic needs of late‐term mother and fetus

Cited by 4 publications

References 60 publications

Untargeted Metabolome Analysis Reveals Reductions in Maternal Hepatic Glucose and Amino Acid Content That Correlate with Fetal Organ Weights in a Mouse Model of Fetal Alcohol Spectrum Disorders

Untargeted Metabolome Analysis Reveals Reductions in Maternal Hepatic Glucose and Amino Acid Content That Correlate with Fetal Organ Weights in a Mouse Model of Fetal Alcohol Spectrum Disorders

Untargeted Metabolome Analysis of Alcohol-Exposed Pregnancies Reveals Metabolite Differences That Are Associated with Infant Birth Outcomes

A metabolomic study on the effect of prenatal exposure to Benzophenone-3 on spontaneous fetal loss in mice

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