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Table 1.

The birth and brain weight of the collected control and IUGR rabbit fetuses.

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Figure 1.

Metabolic differences between control and IUGR fetal brain tissue.

Bar charts show the measured metabolite ion intensities of NAAG, NAA, pyroglutamic acid (A), ornithine, L-lysine, aspargine, histidine and 2-keto-isovalerate (B), succinate, panthothenate, malondialdehyde, 3-nitrotyrosine, purine and 3,4-Dihydroxybutyric acid (C), GMP, DHA, palmitoleic acid and oleic acid (D) in control (white bars) and IUGR (black bars) fetal brain tissue. All metabolite ion intensities were significantly different (p<0.05) based on a t-test followed by a Benjamini-Hochberg Multiple Testing Correction. Data are presented as mean, control (n = 5) and IUGR (n = 4) fetal brains with error bars representing standard deviation.

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Table 2.

Metabolites with significantly different ion intensities in control and IUGR fetal brain tissue.

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Figure 2.

Principal Component Analysis (PCA) score plot showed a clear cluster separation of the control (blue) and IUGR (red) fetal brain tissue samples.

The PCA was based on the significant metabolites identified by the t-test. The plot shows the first three principal components that include PC1∶49.83%, PC2∶12.77% and PC3∶9.23% percentage of total variables.

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Figure 3.

Dendrogram and heatmap showing the metabolic differences between control and IUGR fetal brain tissue samples.

The significantly altered metabolites were hierarchically clustered (columns) and ratios plotted on a color scale (rows). The dendrogram showed a clear cluster formation between the control (blue) and IUGR (red) samples. In addition, smaller clusters are visible, which mostly group the hemisphere anterior (HA), hemisphere posterior (HP) basal ganglia (BG) and brain stem (BS) regions.

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Table 3.

The X-loading values for the first principal component of the PCA score plot.

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Figure 4.

Correlation graphs between fetal birth weight and metabolite ion intensities.

The metabolites aspargine (r2 = 0.6723) (A), ornithine (r2 = 0.5422) (B), palmitoleic acid (r2 = 0.4938) (C) and NAAG (r2 = 0.3712) (D) showed the highest correlation coefficient. Brain tissue samples from IUGR fetus with the highest birth weight (I), showed metabolite intensities more similar to the controls. Each point represents a single fetal brain tissue sample.

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