scholarly journals The conceptus increases secreted phosphoprotein 1 gene expression in the mouse uterus during the progression of decidualization mainly due to its effects on uterine natural killer cells

Reproduction ◽  
2007 ◽  
Vol 133 (6) ◽  
pp. 1213-1221 ◽  
Author(s):  
Jennifer L Herington ◽  
Brent M Bany
Keyword(s):  
Gene Expression ◽  
Natural Killer ◽  
Killer Cell ◽  
Cell Types ◽  
Mouse Uterus ◽  
Cell Functions ◽  
Uterine Natural Killer Cells ◽  
Unk Cells ◽  
Secreted Phosphoprotein 1 ◽  
Uterine Natural Killer

Within the mouse endometrium, secreted phosphoprotein 1 (SPP1) gene expression is mainly expressed in the luminal epithelium and some macrophages around the onset of implantation. However, during the progression of decidualization, it is expressed mainly in the mesometrial decidua. To date, the precise cell types responsible for the expression in the mesometrial decidua has not been absolutely identified. The goal of the present study was to assess the expression of SPP1 in uteri of pregnant mice (decidua) during the progression of decidualization and compared it with those undergoing artificially induced decidualization (deciduoma). Significantly (P<0.05) greater steady-state levels of SPP1 mRNA were seen in the decidua when compared with deciduoma. Further, in the decidua, the majority of the SPP1 protein was localized within a subpopulation of granulated uterine natural killer (uNK) cells but not co-localized to their granules. However, in addition to being localized to uNK cells, SPP1 protein was also detected in another cell type(s) that were not epidermal growth factor-like containing mucin-like hormone receptor-like sequence 1 protein-positive immune cells that are known to be present in the uterus at this time. Finally, decidual SPP1 expression dramatically decreased in uteri of interleukin-15-deficient mice that lack uNK cells. In conclusion, SPP1 expression is greater in the mouse decidua when compared with the deciduoma after the onset of implantation during the progression of decidualization. Finally, uNK cells were found to be the major source of SPP1 in the pregnant uterus during decidualization. SPP1 might play a key role in uNK killer cell functions in the uterus during decidualization.

scholarly journals α-actin Down Regulation and Perforin Loss in Uterine Natural Killer Cells From LPS-Treated Pregnant Mice

2015 ◽  
pp. 427-432 ◽  
Author(s):  
B. ZAVAN ◽  
A. M. DO AMARANTE-PAFFARO ◽  
V. A. PAFFARO
Keyword(s):  
Natural Killer ◽  
Cell Types ◽  
Normal Pregnancy ◽  
Down Regulation ◽  
Uterine Arteries ◽  
Uterine Natural Killer Cells ◽  
Unk Cells ◽  
Pregnant Mice ◽  
Unk Cell ◽  
Uterine Natural Killer

One of the most abundant immunologic cell types in early decidua is the uterine natural killer (UNK) cell that despite the presence of cytoplasmic granules rich in perforin and granzymes does not degranulate in normal pregnancy. UNK cells are important producers of angiogenic factors that permit normal dilation of uterine arteries to provide increased blood flow for the growing feto-placental unit. Gram-negative bacteria lipopolysaccharide (LPS) administration can trigger an imbalance of pro-inflammatory and anti-inflammatory cytokines impairing the normal immune cells activity as well as uterine homeostasis. The present study aimed to evaluate by immunohistochemistry the reactivity of perforin and α-actin on UNK cell from LPS-treated pregnant mice. For the first time, we demonstrate that LPS injection in pregnant mice causes α-actin down regulation, concomitantly with perforin loss in UNK cells. This suggests that LPS alters UNK cell migration and activates cytotoxic granule release.

scholarly journals Proliferation of Uterine Natural Killer Cells Is Induced by Human Chorionic Gonadotropin and Mediated via the Mannose Receptor

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2882-2888 ◽  
Author(s):  
Nicole Kane ◽  
Rodney Kelly ◽  
Philippa T. K. Saunders ◽  
Hilary O. D. Critchley
Keyword(s):  
Natural Killer ◽  
Mannose Receptor ◽  
Lh Receptor ◽  
Uterine Natural Killer Cells ◽  
Unk Cells ◽  
The Impact ◽  
Insight Into ◽  
Unk Cell ◽  
Uterine Natural Killer

The endometrial lining of the human uterus contains a population of phenotypically distinct (CD56bright, CD16dim), tissue-specific, natural killer [uterine natural killer (uNK)] cells that play a key role in the establishment of a successful pregnancy. An increase in the number of endometrial uNK cells occurs when the conceptus implants, and there is a further increase during the early stages of placentation. Here, we describe studies that have identified human chorionic gonadotrophin (hCG), a glycoprotein synthesized by the preimplantation conceptus, as a novel regulator of uNK cell proliferation. The impact of hCG on uNK cells was mediated via the mannose receptor (CD206) rather than by the classical hCG/LH receptor that was not expressed. The mannose receptor and hCG were colocalized on the surface of uNK cells, and proliferation did not occur if cells were incubated with deglycosylated hCG or intact hCG in the presence of excess d-Mannose. These novel observations provide new insight into the endocrine-immune dialogue that exists between the conceptus and immune cells within the receptive endometrium, and have implications for the role of uNK cell-trophoblast interactions and pregnancy outcome.

1.  Heme Oxygenase‐1 Enzyme Deficiency Affects Uterine Natural Killer Cell Function During Murine Pregnancy 

2017 ◽  
Author(s):  
Tracy Zhang
Keyword(s):  
Natural Killer ◽  
Heme Oxygenase ◽  
Cell Function ◽  
Recurrent Miscarriage ◽  
Embryo Implantation ◽  
Killer Cell ◽  
Implantation Site ◽  
Heme Oxygenase 1 ◽  
Unk Cells ◽  
Uterine Natural Killer

Recurrent miscarriage is a condition that affects 1% of all women, and rejection of the fetus by the mother's immune system is thought to be one of the underlying causes. The mechanisms of maternal tolerance vital to a successful pregnancy are not well understood; however, uterine natural killer (uNK) cells are implicated as they comprise over 70% of immune cells in the uterus during early pregnancy. Heme oxygenase‐1 (HO‐1) is an enzyme that is known to be immunosuppressive. Moreover, mice missing HO‐1 have extremely high abortion rates. This study is the first to analyze the effects of HO‐1 deficiency specifically on uNK cells. We posit that an absence of HO‐1 affects normal uNK cell‐mediated immunosuppression, and also possibly their ability to modify uterine spiral arteries supplying blood to the fetus. Our study analyzed embryos from mice lacking or deficient in HO‐1 on days 8, 10, and 12 of pregnancy. Both number of uNK cells and degree of vascularization were analyzed using immunohistochemistry staining. We observed a significantly higher number of uNK cells in one area of the embryo implantation site and a significantly lower number of cells in another, suggesting the uNK cells are failing to localize properly. Analysis of vascularization is currently ongoing. Since women with multiple miscarriages have been shown to down‐regulate HO‐1, confirmation that absence of HO‐1 leads to implantation site abnormalities could pave the way for future clinical treatments.  

scholarly journals The Roles of Uterine Natural Killer (NK) Cells and KIR/HLA-C Combination in the Development of Preeclampsia: A Systematic Review

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xiuhua Yang ◽  
Yahui Yang ◽  
Yiru Yuan ◽  
Lin Liu ◽  
Tao Meng
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Systemic Disease ◽  
Killer Cell ◽  
Inflammatory Factors ◽  
Placental Development ◽  
Multiple Organs ◽  
Unk Cells ◽  
Exact Etiology ◽  
Uterine Natural Killer

Preeclampsia (PE) is termed as a systemic disease that involves multiple organs; however, the exact etiology is still quite unclear. It is believed that the poor remodeling of uterine spiral arteries triggers PE, thereby causing failed placentation and producing inflammatory factors. The decline of blood flow results in lowering the nutrients and oxygen received by the fetus and augmenting the placental pressure in PE. Decidual immune cells, especially uterine natural killer (uNK) cells, are involved in the process of placentation. Decidual NK (dNK) cells significantly contribute to the vascular remodeling through the secretion of cytokines and angiogenic mediators in normal placental development. The abnormal activation of NK cells in both the peripheral blood and the decidua was counted among the causes leading to PE. The correlation existing between maternal killer cell immunoglobulin-like receptor (KIR) and HLA-C in trophoblast cells constitutes a robust evidence for the genetic etiology of PE. The combinations of the two kinds of gene systems, together with the KIR genotype in the mother and the HLA-C group in her fetus, are likely to exactly decide the pregnancy outcome. The women, who have the inappropriate match of KIR/HLA-C, are likely to be prone to the augmented risk of PE. However, the combinations of KIR/HLA-C in PE undergo ethnic changes. The extensive prospective research works in Europe, Asia, and Africa are required for providing more findings in PE patients.

scholarly journals Gene Expression Profiling of the Paracrine Effects of Uterine Natural Killer Cells on Human Endometrial Epithelial Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Xin Gong ◽  
Zhenzhen Chen ◽  
Yanxia Liu ◽  
Qiudan Lu ◽  
Zhe Jin
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Natural Killer ◽  
Paracrine Effects ◽  
Unk Cells ◽  
Interleukin 15 ◽  
Factor C ◽  
Unk Cell ◽  
Endometrial Epithelial Cells ◽  
Uterine Natural Killer

The endometrium contains a population of immune cells that undergo changes during implantation and pregnancy. The majority of these cells are uterine natural killer (uNK) cells; however, it is unclear how these cells interact with endometrial epithelial cells. Therefore, we investigated the paracrine effects of the uNK cell-secretion medium on the gene expression profile of endometrial epithelial cellsin vitrothrough microarray analysis. Our results, which were verified by qRT-PCR and western blot, revealed that soluble factors from uNK cells alter the gene expression profiles of epithelial cells. The upregulated genes included interleukin-15 (IL-15) and interleukin-15 receptor alpha (IL-15RA), which result in a loop that stimulates uNK cell proliferation. In addition, vascular endothelial growth factor C (VEGF-C) and chemokine (C-X-C motif) ligand 10 (CXCL-10) were also determined to be upregulated in epithelial cells, which suggests that uNK cells work synergistically with epithelial cells to support implantation and pregnancy. In addition, oriental herbal medicines have been used to treat infertility since ancient times; however, we failed to find that Zi Dan Yin can regulate these endometrial paracrine effects.

scholarly journals Analysis of uterine gene expression in interleukin-15 knockout mice reveals uterine natural killer cells do not play a major role in decidualization and associated angiogenesis

Reproduction ◽  
2012 ◽  
Vol 143 (3) ◽  
pp. 359-375 ◽  
Author(s):  
Brent M Bany ◽  
Charles A Scott ◽  
Kirsten S Eckstrum
Keyword(s):  
Gene Expression ◽  
Natural Killer ◽  
Differential Expression ◽  
Knockout Mice ◽  
Implantation Site ◽  
Wild Type ◽  
Rt Pcr ◽  
Unk Cells ◽  
Interleukin 15 ◽  
Uterine Natural Killer

During decidualization, uterine natural killer (uNK) cells are the most abundant immune cell types found in the uterus. Although it is well known that they play key roles in spiral arteriole modification and the maintenance of decidual integrity seen after mid-pregnancy, their roles in the differentiation of decidual cells and accompanying angiogenesis during the process of decidualization is less well characterized. To address this, we used whole-genome Illumina BeadChip analysis to compare the gene expression profiles in implantation segments of the uterus during decidualization on day 7.5 of pregnancy between wild-type and uNK cell-deficient (interleukin-15-knockout) mice. We found almost 300 differentially expressed genes and verified the differential expression of ∼60 using quantitative RT-PCR. Notably, there was a lack of differential expression of genes involved in decidualization and angiogenesis and this was also verified by quantitative RT-PCR. Similar endothelial cell densities and proliferation indices were also found in the endometrium between the implantation site tissues of wild-type and knockout mice undergoing decidualization. Overall, the results of this study reveal that uNK cells likely do not play a major role in decidualization and accompanying angiogenesis during implantation. In addition, the study identifies a large number of genes whose expression in implantation-site uterine tissue during decidualization depends on interleukin-15 expression in mice.

Sign in / Sign up

Export Citation Format

Share Document