Obstetrics and Gynaecology - Theses

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Type: Masters Research thesis × Subject: ageing, decidual mesenchymal stem/stromal cells, labour, functional analyses, lipid analyses, stem cells ×

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    The role of decidual mesenchymal stem/stromal cell ageing in labour
    Wijaya, Joan Christie ( 2019)
    Ageing and parturition share many common pathways, but whether these two processes are associated, or even dependent on each other, is poorly understood. This study focuses on the decidua, where there is evidence that decidual cells undergo ageing as parturition approaches term, and these ageing-related changes of the decidua may trigger labour. Mesenchymal stem/stromal cells (MSCs) are a type of stem cell that reside in the decidua. Ageing of decidual MSCs (DMSCs) may contribute to the functional and molecular changes in decidual tissue required for spontaneous onset of labour (SOL) at term. The objective of this study was to determine whether DMSCs from patients experiencing SOL show evidence of molecular and functional loss and/or changes compared with DMSCs from patients, not in labour (NIL), undergoing Caesarean section (C-section) delivery. Placentae were collected from full-term (39-40 week gestation), SOL (n = 8) and NIL (n = 7) patients with non-complicated pregnancies. DMSCs were isolated from decidua basalis, which remains attached to the placentae following delivery. DMSCs were characterised to ensure their decidua-origin and stem cell properties. Important cell functions, including cell proliferation, cell migration, cell death, lipid peroxidation, aldehyde dehydrogenase (ALDH) expression, and pro-inflammatory cytokine secretion were then compared between SOL- and NIL-DMSCs. SOL-DMSCs demonstrated a significant increase in necrosis, lipid peroxidation, migration, and IL-6 production compared with NIL-DMSCs (p < 0.05). SOL-DMSCs also showed an increase in apoptosis as well as a decrease in proliferation, ALDH expression and IL-8 production compared with NIL-DMSCs, however, the differences were not statistically significant (p > 0.05). These findings suggested that SOL-DMSCs underwent advanced ageing at term. The lipid contents of DMSCs from both patient groups were extracted using Folch’s method, separated using High Performance Liquid Chromatography (HPLC) and identified using tandem mass spectrometry (MS/MS). The quantity of each lipid species from DMSCs of both patient groups was measured and compared. SOL- and NIL-DMSCs contained the same lipid species, however the expression level of particular lipid species significantly differed. DMSCs may undergo changes in lipid metabolism during labour at term, possibly to provide the energy source for the labour process. In conclusion, this study provides novel evidence that DMSCs undergo ageing-related functional and molecular changes associated with labour and these changes may play a significant role in promoting spontaneous labour at term.