Maternal Nutrient Restriction Disrupts Gene Expression and Metabolites Associated with Urea Cycle, Steroid Synthesis, Glucose Homeostasis, and Glucuronidation in Fetal Calf Liver

Figures

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  Figure 1. Heatmap of HCA using the top 50 statistically different liver metabolites between LN (green) and HN (red) fetuses. The row displays the metabolite, and the column represents the sample. Metabolites with relatively low contents are displayed in blue, while metabolites with relatively high contents are displayed in right brown. The brightness of each color corresponds to the magnitude of the difference when compared with the average value. FormiminoGA; formiminoglutamic acid, BTL; betaine aldehyde, 3-APRP-1,2-diol; 3-aminopropane-1,2-diol, N-AcGlu; N-acetyl glutamate, CMP; cytidine monophosphate, CoA; coenzyme A, 3′-AMP; 3′-adenosine monophosphate, GSSG; oxidized glutathione, GlcN/GalN; N-acetylglucosamine/N-acetylgalactosamine, GlcA/GalA; glucosamine/galactosamine, 2-HBA; 2-hydroxybutyrate, GlcNa/GalNa/ManNa; N-acetylglucosamine/N-acetylgalactosamine/N-acetylmannosamine, UDP-glucuronate; uridine 5′-diphosphate-glucuronate, 4-amino-3-HBA; 4-amino-3-hydroxybutyrate, 2-AEP; 2-aminoethylphosphonate, FAD; flavin adenine dinucleotide, 3-hydroxy-3-MGA; 3-hydroxy-3-methylglutarate, UDP-Glc/UDP-Gal; UDP-glucose/UDP-galactose. Amino acids and peptides are shown in three letter code.

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  Figure 2. Heatmap of HCA using 201 differentially expressed genes (p ≤ 0.05) between the LN (green) and HN (red) fetal livers. The row displays the gene and the column represents the sample. Genes with relatively low contents are displayed in dark blue, while genes with relatively high contents are displayed in yellow. The brightness of each color corresponds to the magnitude of the difference when compared with the average value.

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  Figure 3. qPCR results of highly down- and upregulated fetal liver genes in microarray analysis. The ratios of the normalized gene expression of the LN (green) to HN (red) fetuses are shown as columns. Ribosomal protein lateral stalk subunit P0 (RPLP0) was used as the internal control. Error bars indicate SEM. **, *, and + indicate differences between the LN and HN fetuses at p ≤ 0.01, ≤0.05, and ≤0.10, respectively. IGFLR1; IGF like family receptor 1, DPP4; dipeptidyl-peptidase 4, PCK1; phosphoenolpyruvate carboxykinase 1, G6PC; glucose-6-phosphatase, catalytic subunit, FKBP1B; FK506 binding protein 1B, QRFPR; pyroglutamylated RFamide peptide receptor, CATHL4; cathelicidin 4.

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  Figure 4. qPCR results of down- and upregulated fetal liver genes associated with essential liver metabolisms. The ratios of the normalized gene expression of the LN (green) to HN (red) fetuses are shown as columns. RPLP0 was used as the internal control. Error bars indicate SEM. **, *, and + indicate differences between the LN and HN fetuses at p ≤ 0.01, ≤0.05, and ≤0.10, respectively. HMGCS2; 3-hydroxy-3-methylglutaryl-CoA synthase 2, ALDOC; aldolase, fructose-bisphosphate C, ENO3; enolase 3, FBP1; fructose-bisphosphatase 1, UGT1A1/UGT1A6/UGT2A1; UDP glucuronosyltransferase family-1 member A1 complex locus/-1 member A6 complex locus/-2 member A1 complex locus, FDPS; farnesyl diphosphate synthase, HSD11B1; hydroxysteroid (11-β) dehydrogenase 1, HSD17B6; hydroxysteroid (17-β) dehydrogenase 6, ANGPTL4; angiopoietin like 4, APOA5; apolipoprotein A-V, EHHADH; enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase, FADS2; fatty acid desaturase 2, ARG2; arginase 2, ASL; argininosuccinate lyase, ASS1; argininosuccinate synthase 1, CPS1; carbamoyl-phosphate synthase 1, ACOX2; acyl-CoA oxidase 2, branched chain, MT1A/MT1E/MT2A; metallothionein-1A/-1E/-2A.

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  Figure 5. Hypothetic scheme of influences of maternal nutrient restriction on the fetal liver molecular pathways and metabolisms. Genes but not metabolites are italicized. Increased and decreased metabolites in the LN fetuses are indicated in red and blue, respectively. Green genes are downregulated in the LN fetuses. Grayed metabolites were not determined in this study.