Author Identifier

Elsa CHEW

https://orcid.org/0000-0001-9030-1189

Date of Award

2024

Document Type

Thesis

Publisher

Edith Cowan University

Degree Name

Master of Medical and Health Science by Research

School

School of Medical and Health Sciences

First Supervisor

David Coall

Second Supervisor

Jemma Berry

Third Supervisor

Mary Lee

Fourth Supervisor

Anna Callan

Abstract

Women who experience hypertensive pregnancy disorders (HPDs) during pregnancy, mainly pre-eclampsia (PE), are four times more likely to develop hypertension after pregnancy and therefore have an increased risk of developing cardiovascular diseases (CVD) in the future. Pregnancy involves a high level of cardiovascular stress and the development of some complications. This has the potential to increase a woman’s susceptibility to vascular or metabolic disease risk in the future. In this research, pre-eclampsia (PE) and pregnancyinduced hypertension (PIH) were representatives of HPDs and were analysed together for the expression of Growth Differentiation Factor-15 (GDF-15) relative to their healthy agematched controls.

GDF-15 is a stress-responsive cytokine related to the Transforming Growth Factor-Beta (TGF ) superfamily. It is also known as a Macrophage Inhibitory Cytokine (MIC)-1, a biomarker for pathological conditions including metabolic disorders. It is hypothesized that GDF15 could be produced by endothelial cells in response to vascular stress and endothelial dysfunction. Furthermore, GDF-15 protein in blood serum has been reported to be induced during inflammation, oxidative stress, ischemia in the heart, in PE and in PIH. Nevertheless, it is important to explore GDF-15 expression not only in blood serum plasma, but also in placental tissue to explore and understand its role in HPD.

The placenta is a vital organ that develops temporarily during pregnancy. It attaches to the lining of the uterus and delivers substantial oxygen and nutrients to the foetus through the umbilical cord. GDF-15 placental mRNA expression was reported to be elevated in PE. Thus, this study hypothesized that GDF-15 expression in the placental tissue is increased in PE and PIH samples as compared to the already present amounts in healthy pregnancy placentae. Therefore, we explored whether placental GDF-15 gene expression was dysregulated in pregnancies complicated by PE and PIH.

Although extensive research has linked serum GDF-15 with metabolic disease which contributes to CVD symptoms, such as acute coronary syndrome, heart failure and pulmonary hypertension (Temel Yuksel et al., 2018), statistically, there was no significant differences observed between the HPD and the control groups for GDF-15 expression in the placental tissue of the mothers in this research study. Therefore, rejecting the hypothesis as suggested previously that, compared to control groups, the placentae of women who experience PIH and PE will have higher levels of GDF-15 expression. However, Pearson’s product-moment correlation showed significant association between maternal BMI with target gene GDF-15 and also maternal weight upon delivery with target gene GDF-15 as realised in the placenta tissue. Thus, this is consistent with findings that suggest a positive correlation between body weight and body fat with GDF-15 expression (Dostálová et al., 2009). The discovery that there was no correlation between GDF-15 expression in the placental tissue of the mothers with HPDs could be because the placental tissue for this study was collected only at delivery. Therefore, there is potential that any treatments sought for the stabilisation of HPD symptoms may have influenced GDF-15 expression levels and removed any likely differences in expression between the groups before this research study was conducted. Nevertheless, this research is a pilot study, it is a first step towards further research to improve our understanding of the relationship between GDF-15 and HPDs. It is crucial for us to understand pregnancy complications in more detail and explore the effects they have on the placenta with the aim of improving reproductive health outcomes.

DOI

10.25958/n0xx-g891

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