Griffiths, M., Marks, H. P., & Young, F. G. (1941). Influence of (Œstrogens and

1. Institute for Life Sciences Pregnancy Induced Changes in the Mouse Liver Transcriptome Leonie R. Grenfell, Samuel P. Hoile, Mark A. Hanson, Karen A. Lillycrop and Graham C. Burdge. Background Leptin levels were significantly increased at d14 (p=0.005). Plasma levels of glucose were found to decrease at d7 before increasing at d18 (p=0.021). No significant differences were found in plasma β-Hb levels. During pregnancy, dramatic metabolic changes occur in response to the growing fetus. These changes have been particularly documented in the rat liver which shows an increase in size during pregnancy (Poo et al., 1939) in response to sex hormones (Griffiths et al., 1941). Despite this, there has been very little further research in to how these alterations are initiated and regulated by the transcriptome. The aim of this study was to characterize changes in gene expression in the liver in relation to the changing metabolic phenotype of the mother. Figure 3. Proportion of genes showing altered gene expression Methods 90 day old (n=>6), C57/Blk6 virgin mice maintained on standard chow were mated and weight gain and 24 hour food intake were measured weekly. Age matched virgin female mice were used as non-pregnant controls. Mice were culled at days 7, 14 and 18 of gestation (d7, d14 and d18) and organs collected. Serum levels of β-hydroxybutyrate (β-Hb), leptin and glucose were measured using colorimetric or ELISA assays. RNA was extracted from liver and transcriptome analysis carried out on the Illumina MouseRef-8 v2.0 Expression BeadChip. Figure 4. Molecular pathways associated with expression changes Results Figure 1. Weight gain and energy intake throughout pregnancy Substantial alteration in the gene expression profile was found at d18 of pregnancy in the liver when compared to non pregnant controls. 43% of the genes found on the array had more than a 2- fold increase or decrease in expression and are associated with fundamental functions across cell proliferation, metabolism and fetal development. As expected, significant weight gain was observed between d7 and d14 (p<0.001), which was sustained until d18 (p<0.001). Food intake also increased at d14 compared to pre-conception (p=0.007), reaching a plateau between d14 and d18. Energy intake increased between conception and d7 (p=0.032) before returning to non-pregnant levels in late gestation. Conclusions Figure 2. Plasma leptin and glucose concentration during pregnancy. These results show that pregnancy induces substantial changes in the regulation of the hepatic transcriptome. Further work will test the hypothesis that such transcriptional changes involve altered epigentic regulation of specific genes References Griffiths, M., Marks, H. P., & Young, F. G. (1941). Influence of (Œstrogens and Androgens on Glycogen Storage in the Fasting Rat. Nature, 147 (3725), 359–359. Poo, L. J., Lew, W., & Addis, T. (1939). Protein Ananbolism of Organs and Tissues During Pregnancy and Lactation. j. Biol. Chem, 128, 69–77. Acknowledgements www.southampton.ac.uk/ifls