Next Article in Journal
FK506 Attenuates the MRP1-Mediated Chemoresistant Phenotype in Glioblastoma Stem-Like Cells
Previous Article in Journal
Soft Coral Dendronephthya puetteri Extract Ameliorates Inflammations by Suppressing Inflammatory Mediators and Oxidative Stress in LPS-Stimulated Zebrafish
Article Menu
Issue 9 (September) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(9), 2696; https://doi.org/10.3390/ijms19092696

Gestational Diabetes Alters the Metabolomic Profile in 2nd Trimester Amniotic Fluid in a Sex-Specific Manner

1
Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2
Center for Research in Reproduction and Women’s Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
3
Division of Endocrinology and Diabetes, The Children’s Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA
4
Department of Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5
AJ Drexel Autism Institute, Drexel University, Philadelphia, PA 19104, USA
6
Penn SRP Center and Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
7
Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
8
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
*
Author to whom correspondence should be addressed.
Received: 7 August 2018 / Revised: 2 September 2018 / Accepted: 6 September 2018 / Published: 10 September 2018
(This article belongs to the Special Issue Risk Factors and Molecular Mechanisms of Gestational Diabetes)
Full-Text   |   PDF [865 KB, uploaded 10 September 2018]   |  

Abstract

Maternal diabetes and obesity induce marked abnormalities in glucose homeostasis and insulin secretion in the fetus, and are linked to obesity, diabetes, and metabolic disease in the offspring, with specific metabolic characterization based on offspring sex. Gestational diabetes (GDM) has profound effects on the intrauterine milieu, which may reflect and/or modulate the function of the maternal–fetal unit. In order to characterize metabolic factors that affect offspring development, we profiled the metabolome of second trimester amniotic fluid (AF) from women who were subsequently diagnosed with gestational diabetes (GDM) using a targeted metabolomics approach, profiling 459 known biochemicals through gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) assays. Using a nested case-control study design, we identified 69 total biochemicals altered by GDM exposure, while sex-specific analysis identified 44 and 58 metabolites in male and female offspring, respectively. The most significant changes were in glucose, amino acid, glutathione, fatty acid, sphingolipid, and bile acid metabolism with specific changes identified based on the offspring sex. Targeted isotope dilution LC/MS confirmatory assays measured significant changes in docosahexaenoic acid and arachidonic acid. We conclude that the sex-specific alterations in GDM maternal–fetal metabolism may begin to explain the sex-specific metabolic outcomes seen in offspring exposed to GDM in utero. View Full-Text
Keywords: gestational diabetes; metabolomics; fetal programming; sex specific effects; amniotic fluid gestational diabetes; metabolomics; fetal programming; sex specific effects; amniotic fluid
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

O’Neill, K.; Alexander, J.; Azuma, R.; Xiao, R.; Snyder, N.W.; Mesaros, C.A.; Blair, I.A.; Pinney, S.E. Gestational Diabetes Alters the Metabolomic Profile in 2nd Trimester Amniotic Fluid in a Sex-Specific Manner. Int. J. Mol. Sci. 2018, 19, 2696.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top