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Investigating a role for imprinted genes in pregnancy complications and the possible influence of maternal lifestyle

Janssen, Anna 2015. Investigating a role for imprinted genes in pregnancy complications and the possible influence of maternal lifestyle. PhD Thesis, Cardiff University.
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Abstract

Imprinted genes, displaying monoallelic parent of origin specific expression, are known to regulate fetal growth and placental development. Work in animal models also suggests that imprinted genes regulate placental hormone signalling to the mother, which is required for induction of maternal adaptation to pregnancy. Aberrant placental imprinted gene expression may therefore have a causative role in pregnancies characterised by abnormal fetal growth and/or inadequate maternal adaptation to pregnancy. Given these important functions, identifying environmental stimuli responsible for perturbed imprinted gene expression is also of interest. This thesis examined human placental expression of the imprinted genes PHLDA2, CDKN1C, PEG3 and PEG10 in three independent cohorts, including pregnancies complicated by fetal growth restriction, fetal overgrowth, preeclampsia, gestational diabetes and maternal mood disorders. Placental imprinted gene expression was also analysed in relation to placental hormone (hPL and PGH) gene expression and in relation to maternal lifestyle factors. The effect of maternal diet on placental imprinted gene expression was further explored in a mouse model to provide evidence for a cause or effect relationship. Placental PHLDA2 expression was significantly increased in growth-restricted pregnancies, supporting a role for PHLDA2 in the negative regulation of fetal growth. In contrast, placental PEG10 expression was positively associated with fetal growth. This study did not support a role for PEG3 in the control of fetal growth, but did suggest a role in maternal adaptation to pregnancy with aberrant gene expression observed in pregnancies complicated by maternal depression. Finally, this study provided evidence that PHLDA2, CDKN1C, PEG3 and PEG10 expression is responsive to environmental stimuli, particularly maternal diet, in both human pregnancies and in a mouse model. Thus, this thesis highlights the importance of imprinted genes in achieving a successful pregnancy for both mother and fetus and the possible role of maternal lifestyle in influencing this.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Biosciences
Date of First Compliant Deposit: 30 March 2016
Last Modified: 05 Jun 2017 05:13
URI: http://orca.cf.ac.uk/id/eprint/80617

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