Nipun Saini1, Manjot Virdee1, Kaylee K Helfrich1,2, Sze Ting Cecilia Kwan1, Susan M Smith3,4. 1. UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC, 28081, USA. 2. Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, NC, 28081, USA. 3. UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC, 28081, USA. Susan_Smith@unc.edu. 4. Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, NC, 28081, USA. Susan_Smith@unc.edu.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Rachel S Kelly; Rachel T Giorgio; Bo L Chawes; Natalia I Palacios; Kathryn J Gray; Hoooman Mirzakhani; Ann Wu; Kevin Blighe; Scott T Weiss; Jessica Lasky-Su Journal: Metabolomics Date: 2017-06-12 Impact factor: 4.290
Authors: Karen L Lindsay; Christian Hellmuth; Olaf Uhl; Claudia Buss; Pathik D Wadhwa; Berthold Koletzko; Sonja Entringer Journal: PLoS One Date: 2015-12-30 Impact factor: 3.240
Authors: Debora Farias Batista Leite; Aude-Claire Morillon; Elias F Melo Júnior; Renato T Souza; Fergus P McCarthy; Ali Khashan; Philip Baker; Louise C Kenny; Jose Guilherme Cecatti Journal: BMJ Open Date: 2019-08-10 Impact factor: 2.692
Authors: Nipun Saini; Manjot S Virdee; Kaylee K Helfrich; Sze Ting Cecilia Kwan; Sandra M Mooney; Susan M Smith Journal: Nutrients Date: 2022-03-05 Impact factor: 6.706