- Title
- The placental renin-angiotensin system in gestational diabetes and its regulation by hyperglycaemia
- Creator
- Lochrin, Alyssa Jade
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2024
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Gestational diabetes mellitus (GDM) is one of the most prevalent complications of pregnancy and has immediate and long-term impacts on maternal and fetal health. It is underpinned by the onset of hyperglycaemia during pregnancy. GDM is associated with several placental abnormalities that could impact placental efficiency and therefore contribute to adverse fetal, neonatal, and maternal outcomes. Hyperglycaemia-induced tissue injury has been comprehensively studied in non-pregnant diabetes, and it is well established that tissue renin-angiotensin systems (RASs) contribute to diabetic tissue pathologies. The expression and activity of major RAS components are enhanced by hyperglycaemia in vitro. RAS signalling can mediate inflammation, fibrosis, and oxidative stress, and we propose that hyperglycaemia-induced activation of the RAS may contribute to the morphological changes in the placenta that are associated with GDM. We know that the placental RAS is an important signalling cascade that exists within the placenta as it regulates cell proliferation, angiogenesis, and trophoblast invasion, and can promote inflammation and fibrosis. In vitro and in vivo studies have demonstrated that dysregulated expression of RAS components alters the function of trophoblasts and adversely impacts placental development and fetal health. It is unknown however, if the expression of the placental RAS is regulated by hyperglycaemia. Very limited research has focused on the mechanisms responsible for the placental alterations in GDM, and the involvement of maternal hyperglycaemia and the placental RAS is yet to be investigated. This thesis is the first set of studies that begin to address this knowledge gap, by investigating the glycaemic regulation of the placental RAS in vitro, and characterising placental and circulating RAS components in uncomplicated pregnancies with normal glucose tolerance (NGT) and pregnancies complicated by GDM in vivo. We demonstrate that hyperglycaemia regulates components of the placental RAS, offering novel insight into the regulation of placental morphology in GDM and other hyperglycaemic conditions of pregnancy such as pre-existing diabetes. This thesis also enhances our understanding of the pathophysiology of GDM, providing novel characterisation of placental and circulating RAS components in GDM pregnancies.
- Subject
- gestational diabetes; renin-angiotensin system; placenta; hyperglycaemia
- Identifier
- http://hdl.handle.net/1959.13/1510612
- Identifier
- uon:56434
- Rights
- Copyright 2024 Alyssa Jade Lochrin
- Language
- eng
- Full Text
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 10 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 308 KB | Adobe Acrobat PDF | View Details Download |