Global metabolomic profiling reveals hepatic biosignatures that reflect the unique metabolic needs of late-term mother and fetus.
Global metabolomic profiling reveals hepatic biosignatures that reflect the unique metabolic needs of late-term mother and fetus.
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DOI：
10.1007/s11306-021-01773-8
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发表时间：
2021-02-07
期刊：
影响因子：
--
通讯作者：
Smith SM
中科院分区：
文献类型：
--
作者：
Saini N;Virdee M;Helfrich KK;Kwan STC;Smith SM
妊娠期疾病包括先兆子痫、生长受限和糖尿病，其部分特征是母亲和胎儿之间的代谢相互作用发生改变。要了解它们的功能相关性，需要在正常条件下进行代谢表征。我们对妊娠、晚期C57BL/6J小鼠(N=9只DAMs)及其胎儿(每窝4胎)的肝脏进行了非靶向代谢组学研究，使用UPLC-MS/MS对730种肝脏代谢物进行了多元分析，发现母体和胎儿的代谢物分布高度区隔，并且在胎儿内(ρ平均值=0.81)或在DAM内(ρ平均值=0.79)比在每个母胎二元体(ρAverage=−0.76)内更相似，这表明与其各自的DAM相比，胎儿肝脏的代谢处于不同的、同样严格的代谢控制之下。代谢物特征与已知的母婴代谢差异相一致。胎儿血糖的降低反映了其糖异生能力有限以及对母体血糖池的依赖。胎儿必需氨基酸的减少和α-酮酸肉碱结合物的升高反映了它们作为第二燃料来源的重要性，以满足胎儿的能量需求。然而，胎儿丝氨酸、甘氨酸、天冬氨酸和谷氨酸的对比升高反映了它们对内源核苷酸合成和胎儿生长的贡献。最后，孕妇肝脏脂质和甘油的升高与分解代谢状态一致，这种状态节省了葡萄糖，以满足相互竞争的母婴能量需求。晚期小鼠DAM和胎儿的代谢物图谱与先前利用血浆和尿液进行的非啮齿动物分析一致。这些数据将小鼠定位为研究母婴代谢如何适应(或不适应)妊娠应激源的机械研究的合适模型。
Gestational disorders including preeclampsia, growth restriction and diabetes are characterized, in part, by altered metabolic interactions between mother and fetus. Understanding their functional relevance requires metabolic characterization under normotypic conditions. We performed untargeted metabolomics on livers of pregnant, late-term C57Bl/6J mice (N=9 dams) and their fetuses (pooling 4 fetuses/litter), using UPLC-MS/MS. Multivariate analysis of 730 hepatic metabolites revealed that maternal and fetal metabolite profiles were highly compartmentalized, and were significantly more similar within fetuses (ρaverage =0.81), or within dams (ρaverage =0.79), than within each maternal-fetal dyad (ρaverage = −0.76), suggesting that fetal hepatic metabolism is under distinct and equally tight metabolic control compared with its respective dam. The metabolite profiles were consistent with known differences in maternal-fetal metabolism. The reduced fetal glucose reflected its limited capacity for gluconeogenesis and dependence upon maternal plasma glucose pools. The fetal decreases in essential amino acids and elevations in their alpha-keto acid carnitine conjugates reflects their importance as secondary fuel sources to meet fetal energy demands. Whereas, contrasting elevations in fetal serine, glycine, aspartate, and glutamate reflects their contributions to endogenous nucleotide synthesis and fetal growth. Finally, the elevated maternal hepatic lipids and glycerol were consistent with a catabolic state that spares glucose to meet competing maternal-fetal energy demands. The metabolite profile of the late-term mouse dam and fetus is consistent with prior, non-rodent analyses utilizing plasma and urine. These data position mouse as a suitable model for mechanistic investigation into how maternal-fetal metabolism adapts (or not) to gestational stressors.
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影响因子：
2
作者：
Ford, Lisa;Kennedy, Adam D.;Toal, Douglas R.
通讯作者：
Toal, Douglas R.
影响因子：
4.7
作者：
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通讯作者：
Herrera, E
影响因子：
3.6
作者：
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通讯作者：
DEVI, BG
影响因子：
8.6
作者：
Dehaven CD;Evans AM;Dai H;Lawton KA
通讯作者：
Lawton KA
DOI：
10.1176/appi.ajp.2018.17070836
发表时间：
2018-07-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Freedman R;Hunter SK;Hoffman MC
通讯作者：
Hoffman MC