The origin and role of uterine natural killer cells in patients with recurrent implantation failure


Khan, Leena The origin and role of uterine natural killer cells in patients with recurrent implantation failure. Master of Philosophy thesis, University of Liverpool.

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Abstract

Recurrent implantation failure (RIF) is the failure of the embryo to implant. Embryonic causes of RIF have been studied intensely; recently, investigations of endometrial causes of RIF have emerged. ‘Natural Killer’ cells appear in large numbers in the endometrium towards the mid-secretory phase, during the ‘window of impanation’. Their role in recurrent implantation failure needs investigating. There are two competing hypotheses regarding the origin of uNK cells. They are either the result of proliferation of resident uNK cells or are from the trafficking of peripheral blood cells into the uterus and their subsequent differentiation into their uNK form. Endometrial biopsies from 19 patients, 10 ‘low’ density uNK and 9 ‘high’ density uNK were stained using immunohistochemisty to compare antibodies associated with trafficking: L-Selectin, with a marker for peripheral blood NK cells, CD16, against makers for proliferation Ki67 and differentiation NKp30, on endometrial tissue, using CD56 as the universal marker for natural killer cells. The endometrial tissue will be obtained 7 days after the LH surge in the luteal phase as this is the window of implantation. Variation in location of these cells within samples was also studied in the following areas: sub-epithelial, areas with low stromal density and perivascular stroma in both groups. Differences in percentage cell density was observed between both groups, as expected. With both groups observing more positively stained cells of each antibody in perivascular areas. Few numbers of CD62-L and CD16+, markers for trafficking cells were detected. This suggests that uNK cells are not migrating in from peripheral blood, but arising from the endometrium, possibly from heamatopoietic cells. CD56+ cells were seen in higher in areas around vessels than in other locations (p=0.003). Their close proximity to vessels enables them to promote vasculature development. The markers for proliferation and differentiation of uNK cells, Ki67 and NKp30 was also significantly higher in areas around vessels compared to areas near epithelium (p=0.006 and p=0.023 respectively). Perhaps this early development of arteries leads to a highly oxygenated state, which is detrimental to the developing embryo. The paucity of trafficking markers indicates that uNK cells are not trafficking from the peripheral blood, so peripheral blood testing is of no clinical value in patients with recurrent implantation failure. The consistent perivascular location of these cells indicates that these proliferating and differentiating cells have a role in vascular remodelling, which, may lead to a highly oxygenated state, decreasing the receptivity of the endometrium and causing implantation failure.

Item Type: Thesis (Master of Philosophy)
Additional Information: Date: 2009-08 (completed)
Subjects: ?? RG ??
Divisions: Faculty of Health and Life Sciences
Depositing User: Symplectic Admin
Date Deposited: 27 Jan 2012 11:20
Last Modified: 16 Dec 2022 04:33
DOI: 10.17638/00001284
Supervisors:
URI: https://livrepository.liverpool.ac.uk/id/eprint/1284
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