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Title: Decidual stromal cell regulation of the maternal-fetal interface in early pregnancy
Author: James-Allan, Laura B.
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2016
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Abstract:
Decidualisation is the differentiation of endometrial stromal cells in to specialised secretory decidual stromal cells (DSC), which commences in the mid-secretory phase of the menstrual cycle and continues in pregnancy. During placentation, DSC regulate and control the invasion of extravillous trophoblast cells (EVT). In the decidua there is cross-talk between DSC and EVT and immune cells. The effect of DSC secreted factors on EVT and immune cell function in the first trimester of pregnancy was investigated. Pre-eclampsia is associated with inadequate trophoblast invasion and spiral artery remodelling. Uterine artery Doppler resistance index (RI) is used as a proxy measure of spiral artery remodelling. Pregnancies with a high RI are at increased risk of developing pregnancy complications, such as pre-eclampsia. The phenotype and function of DSC from normal and high RI pregnancies was compared. First trimester DSC were isolated from the decidua of terminations of pregnancy (n=93); these cells were able to re-decidualise in vitro. Conditioned media (CM) generated from normal and high RI DSC was used to study the effect of DSC-secreted factors on EVT and immune cell function. Results indicated that DSC CM from either normal or high RI pregnancies had no significant effects on EVT motility, proliferation or apoptosis. However, DSC CM from high RI pregnancies inhibited EVT chemotaxis (n=6, /?=0.046). Luminex array results demonstrated that DSC secrete an array of factors, however no difference was observed between normal and high RI DSC. DSC CM significantly stimulated decidual natural killer (dNK) cell IL-8 (n=T8,/?<0.0001) and IL-6 (n=18, /?=0.001) secretion but did not alter dNK or decidual macrophage receptor expression. In conclusion first trimester DSC secrete a wide range of factors that have roles in regulating trophoblast chemotaxis and dNK cell cytokine secretion. Although DSC secreted factors from pregnancies with a higher risk of pre-eclampsia were not altered, inhibited trophoblast chemotaxis may be contributing to abnormal placentation observed in conditions where remodelling is impaired, such as pre-eclampsia.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.719155  DOI: Not available
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