TY - JOUR
T1 - Gestational diabetes alters the metabolomic profile in 2nd trimester amniotic fluid in a sex-specific manner
AU - O’Neill, Kathleen
AU - Alexander, Jacqueline
AU - Azuma, Rikka
AU - Xiao, Rui
AU - Snyder, Nathaniel W.
AU - Mesaros, Clementina A.
AU - Blair, Ian A.
AU - Pinney, Sara E.
N1 - Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018/9/10
Y1 - 2018/9/10
N2 - 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.
AB - 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.
KW - Amniotic fluid
KW - Fetal programming
KW - Gestational diabetes
KW - Metabolomics
KW - Sex specific effects
UR - http://www.scopus.com/inward/record.url?scp=85053314263&partnerID=8YFLogxK
U2 - 10.3390/ijms19092696
DO - 10.3390/ijms19092696
M3 - Article
C2 - 30201937
AN - SCOPUS:85053314263
SN - 1661-6596
VL - 19
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 9
M1 - 2696
ER -
