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

Gestational Diabetes Alters the Metabolomic Profile in 2nd Trimester Amniotic Fluid in a Sex-Specific Manner.
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DOI:
10.3390/ijms19092696
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发表时间:
2018-09-10
影响因子:
5.6
通讯作者:
Pinney SE
Pinney SE
中科院分区:
生物学2区
文献类型:
--
作者:
O'Neill K;Alexander J;Azuma R;Xiao R;Snyder NW;Mesaros CA;Blair IA;Pinney SE

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母体糖尿病和肥胖症诱导胎儿葡萄糖稳态和胰岛素分泌的显著异常,并与后代的肥胖症、糖尿病和代谢疾病相关,具有基于后代性别的特定代谢特征。妊娠期糖尿病(GDM)对宫内环境有着深远的影响,它可以反映和/或调节母胎单位的功能。为了表征影响后代发育的代谢因素,我们使用靶向代谢组学方法分析了随后诊断为妊娠期糖尿病(GDM)的妇女的孕中期羊水(AF)的代谢组,通过气相色谱/质谱(GC/MS)和液相色谱/质谱(LC/MS)测定分析了459种已知生化物质。使用巢式病例对照研究设计,我们确定了69个总的生物化学物质改变GDM暴露,而性别特异性分析确定了44和58代谢产物的男性和女性后代,分别。最显著的变化是葡萄糖、氨基酸、谷胱甘肽、脂肪酸、鞘脂和胆汁酸代谢,根据后代性别确定了特定变化。靶向同位素稀释LC/MS确证性测定测量二十二碳六烯酸和花生四烯酸的显着变化。我们的结论是,性别特异性改变GDM母胎代谢可能开始解释性别特异性代谢的后代暴露于GDM子宫内的结果。
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.
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