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Title: The role of decidual macrophages in the first trimester of pregnancy and in the pregnancy complication pre-eclampsia
Author: Buckley, Rebecca J.
ISNI:       0000 0004 6349 7763
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2016
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Uterine decidual macrophages are present throughout pregnancy however, little is known of their phenotype or functional relevance. This study aimed to further the understanding of decidual macrophage phenotype and function across the first and early second trimester. In addition, this study aimed to compare decidual macrophages derived from normal pregnancies and those at increased risk of developing complications (pre-eclampsia, FGR and stillbirth). Macrophage phenotype was shown to differentially affect trophoblast behaviour, with pro-inflammatory (M1 -like) macrophages inducing trophoblast apoptosis and impairing trophoblast motility, proliferation and network formation, when compared with an anti-inflammatory (M2-like) phenotype. Decidual macrophages were found to become increasingly anti-inflammatory with gestation; with upregulation of CD206 expression and downregulation of CD86, TLR4 and CD11c expression between the 4th and 14th week of pregnancy. The relative risk of a pregnancy developing complications was calculated by uterine artery resistance indices (Rl) measured by Doppler Ultrasound scanning, enabling phenotypic and functional comparisons to be made between decidual macrophages from normal and higher risk pregnancies. Decidual macrophages from normal pregnancies and those with a higher risk were found to differ in their cytokine secretion profiles, with those from higher risk pregnancies having reduced TNF-a, IL-8, VEGF, IL-1 ra and M-CSF secretion. Decidual macrophages from pregnancies with a higher risk of developing complications were also found to increase trophoblast apoptosis, reduce trophoblast proliferation, and impair trophoblast chemotaxis and network formation, when compared to decidual macrophages from normal pregnancies. Vascular smooth muscle apoptosis, proliferation and motility was not found to be affected by decidual macrophages. When decidual NK cells were cultured with secreted factors from decidual macrophages no effect on decidual NK phenotype was observed. Conversely, decidual macrophages cultured with decidual NK cell secreted factors were found to have elevated expression of CD11c and TLR4. The shift in decidual macrophage phenotype with advancing gestation likely reflects the requirement for tolerance of the semi-allogeneic fetus to support a successful pregnancy. The differential regulatory effect of decidual macrophages from normal and higher risk pregnancies on trophoblast phenotype and function are particularly interesting given that aberrant trophoblast invasion and spiral artery remodelling is related to the pathology of pre-eclampsia. These observations suggest that pre­eclampsia is preceded by impaired decidual macrophage-trophoblast interactions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available