[Truncated abstract] Glucocorticoids are critical for the maturation of the fetus late in pregnancy. Indeed, clinical administration of glucocorticoids is used to accelerate fetal lung maturation in mothers at risk of pre-term delivery. Increased glucocorticoid exposure, however, can have detrimental effects on fetal and placental growth and increase the risk of disease in later life. Many studies have focused on the effect of an increase in the transplacental passage of glucocorticoids on both fetal growth and subsequent postnatal development. But there is a growing body of evidence to suggest that the impact of glucocorticoids on fetal growth is mediated, in part, via their direct effects on the placenta . . . Overall, these studies quantify the labyrinth zone-specific increases in placental expression of PPARG and VEGF in association with a marked increase in vascularisation observed near term. Furthermore, this study demonstrates for the first time that these increases in gene expression are prevented by maternal dexamethasone treatment which also inhibits growth of the fetal capillary network. Elevated expression of SFRP4 in the regressing basal zone late in gestation and in both placental zones after dexamethasone-induced placental growth restriction is consistent with a role for SFRP4 in glucocorticoid-mediated inhibition of wnt signalling. Collectively, the data presented in this thesis show that glucocorticoid inhibition of fetal growth is mediated in large part via effects on the placenta, specifically through inhibition of signals that promote proliferation and vascularisation.
| Identifer | oai:union.ndltd.org:ADTP/221456 |
| Date | January 2007 |
| Creators | Hewitt, Damien Phillip |
| Publisher | University of Western Australia. School of Anatomy and Human Biology |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Copyright Damien Phillip Hewitt, http://www.itpo.uwa.edu.au/UWA-Computer-And-Software-Use-Regulations.html |
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