Review: Functional role of uterine natural killer (uNK) cells in human early pregnancy decidua
Introduction
Two of the key processes in the establishment of a successful human pregnancy are invasion of extravillous trophoblast (EVT) into uterine decidua and inner myometrium and remodeling of uterine spiral arteries. Failure or inadequate completion of these processes has been linked with several severe complications of pregnancy, including second trimester miscarriage [1], pre-eclampsia [2], preterm delivery [3] and fetal growth restriction [4]. Regulation of both of these processes remains incompletely understood, although it is likely to require a balance between factors deriving from the trophoblast and those from within the decidua itself. Leukocytes, namely uterine natural killer (uNK) cells, macrophages, T lymphocytes and dendritic cells, comprise around 30–40% of the cells within the decidual stroma in early pregnancy (reviewed in [5]). The uNK cells are the most numerous of these leukocytes in early pregnancy and recently have been shown to play a role both in regulating trophoblast invasion and in spiral artery remodeling [6], [7]. The proposed functions of uNK cells are the focus of this review.
Section snippets
Uterine natural killer cells
Uterine natural killer (uNK) cells are the most abundant decidual leukocytes and account for approximately 70% of stromal CD45-positive cells in the first trimester of human pregnancy. In the early histological descriptions, uNK cells were most often characterised by the presence of phloxinophilic cytoplasmic granules in the phloxine tartrazine stain and were proposed to derive from endometrial stromal cells [8]. After confirmation that they were leukocytes [9], they were also confirmed as an
Functional investigations
Functional studies of endometrial and decidual leukocytes have focused particularly on uNK cells, especially since these cells have been identified as the major endometrial leukocyte population around the time of implantation and in early pregnancy.
Conclusions
Over the last few years several studies have demonstrated significant roles for uNK cells in immunotolerance, regulation of EVT invasion and spiral artery remodeling. Data from our laboratory suggests that uNK cells from different stages of early pregnancy may play different roles based on their angiogenic growth factor and cytokine profiles (Fig. 2). We suggest that prior to 10 weeks gestational age uNK cells play a role in the initial stages of ‘trophoblast independent’ spiral artery
Conflict of interest
The authors do not have any potential or actual personal, political, or financial interest in the material, information, or techniques described in this paper.
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