UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC, 28081, USA.
Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, NC, 28081, USA.
Metabolomics. 2021 Feb 7;17(2):23. doi: 10.1007/s11306-021-01773-8.
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 (ρ = 0.81), or within dams (ρ = 0.79), than within each maternal-fetal dyad (ρ = - 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.
妊娠疾病包括子痫前期、生长受限和糖尿病的部分特征是母体和胎儿之间代谢相互作用的改变。了解它们的功能相关性需要在正常表型条件下进行代谢特征分析。
我们使用 UPLC-MS/MS 对妊娠晚期 C57Bl/6J 小鼠（N=9 只母鼠）及其胎儿（每窝 4 只胎儿混合）的肝脏进行非靶向代谢组学分析。
对 730 种肝脏代谢物的多变量分析表明，母鼠和胎儿的代谢物谱高度分隔，并且在胎儿内（ρ=0.81）或在母鼠内（ρ=0.79）比在每个母胎对内（ρ=-0.76）更为相似，这表明与相应的母鼠相比，胎儿的肝代谢受到独特且同样严格的代谢控制。代谢物谱与母胎代谢的已知差异一致。胎儿葡萄糖减少反映了其有限的糖异生能力和对母体血浆葡萄糖池的依赖。胎儿必需氨基酸减少和其α-酮酸肉碱轭合物增加反映了它们作为次要燃料来源以满足胎儿能量需求的重要性。相反，胎儿丝氨酸、甘氨酸、天冬氨酸和谷氨酸的升高反映了它们对内源性核苷酸合成和胎儿生长的贡献。最后，母体肝脏脂质和甘油的升高与分解代谢状态一致，该状态将葡萄糖节省下来以满足母体-胎儿的竞争能量需求。
晚期小鼠母鼠和胎儿的代谢物谱与利用血浆和尿液进行的先前非啮齿动物分析一致。这些数据表明，小鼠是一种适合用于研究母体-胎儿代谢如何适应（或不适应）妊娠应激的机制的模型。
