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The role and origin of uterine natural killer cells in patients with unexplained recurrent miscarriage

Karam, Asiyah (2009) The role and origin of uterine natural killer cells in patients with unexplained recurrent miscarriage. Masters thesis, University of Liverpool.

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Abstract

The aim of the study was to determine the role of uNK cells by looking at their numbers across three location sites, the epithelial edge, areas of low stromal cell density/oedema and peri-vascular stroma/spiral arteries. The universal NK cell marker, CD56 was used to identify uNK cells in the endometrium. The research determined whether uNK cells were the result of proliferation and differentiation of resident uNK cells or trafficking of pbNK cells. In addition, it was determined whether uNK cells play a part in spiral artery remodelling and trophoblast invasion and also the role they may play in RM. The hypothesis was tested using Immunohistochemical staining on serial sequential sections of endometrial tissue received from RM patients of extreme phenotype between LH + 5-9 days. Analysis was made on 20 RM patients, 10 patients were grouped as high uNK, defined as an uNK cell density value of ≥ 5% and 10 were grouped as low uNK, defined as an uNK cell density value of ≤ 2.5%. The endometrial samples were stained for the antibodies to CD56, KI67, NKp30, L-Selectin and CD16, uNK cell markers of proliferation, differentiation and trafficking. No association was found between RM and age. The high uNK density group had significantly higher levels for all the antibodies stained (P<0.0001). uNK cells were more proliferative and differentiated in the high uNK cell density group compared to the low. Proliferative and differentiated uNK cells also varied significantly across the location sites (P=0.003 and P=0.008 respectively). A significantly increased number of uNK cells staining positive for CD56, KI67 and NKp30 were found clustered around vessels (P=0.021, 0.001 and P=0.004 respectively). The paucity of L-Selectin+ and CD16+ stained cells in both groups, low and high uNK cell density suggests that uNK cells are not trafficking from peripheral blood. Also, the spatial and temporal relationship of proliferative and differentiated uNK cells suggests that uNK cells originate from resident endometrial NK cells and do not arise from peripheral blood. In addition, KI67+ and NKp30+ uNK cells may assist with angiogenesis of uterine spiral arteries, which in turn increases uterine artery blood flow and subsequently initiates oxidative stress in the early developing foetus leading to RM.

Item Type:Thesis (Masters)
Subjects:R Medicine > RG Gynecology and obstetrics
Departments, Research Centres and Related Units:Academic Faculties, Institutes and Research Centres > Faculty of Medicine > School of Reproductive & Developmental Medicine
Refereed:Yes
Status:Unpublished
ID Code:1280
Deposited On:27 Jan 2012 11:04
Last Modified:30 Jan 2012 02:15

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