Promotion of Angiogenesis by Human Endometrial Lymphocytes

Dunk, Caroline; Smith, Samantha D.; Hazan, Aleah; Whittle, Wendy; Jones, Rebecca L.

doi:10.1080/08820130802191466

Cited by 27 publications

(19 citation statements)

References 149 publications

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“…Alterations in gene expression in this period could compromise these processes which in turn may be critical for subsequent embryo implantation during the secretory phase. 29 Distinct genes that modulate growth and induce cell proliferation were upregulated in the midproliferative phase. Surprisingly, genes normally associated with implantation are expressed here as well.…”

Section: Discussionmentioning

confidence: 99%

Global Gene Expression Profiling of Proliferative Phase Endometrium Reveals Distinct Functional Subdivisions

et al. 2012

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The human endometrium follows a predictable pattern of development during the proliferative phase. Endometrial thickness increases after day 3 and then plateaus at days 9 to 10 of the menstrual cycle despite continued high serum levels of estrogen. We hypothesized that proliferative phase endometrium undergoes more than simple estrogen responsive growth, rather it is characterized by complex time-dependent functional activities reflected in differential gene expression. Nine endometrial RNA samples from healthy participants were subjected to microarray analysis and 15 samples were used for quantitative real-time polymerase chain reaction. The samples were divided into early, mid, or late proliferative phase. The early proliferative phase showed higher expression of genes including transforming growth factor b2, chemokine (C-C motif) ligand 18 (CCL18), and metallothionein 2A. The mid-proliferative phase was characterized by higher expression of heat shock proteins and implantation-associated genes including Indian hedgehog, secreted frizzled protein 4, and progesterone receptor. In the late proliferative phase, we identified increased angiotensin II receptor, type 2 and large decrease in expression of genes related to natural killer (NK) cell function. We demonstrate a unique gene expression signature at distinct time points within the proliferative phase. The early proliferative phase is characterized by tissue remodeling, angiogenesis, and modulation of inflammation; the mid-proliferative phase is characterized not only by proliferation in response to estrogens but also marks the onset of expression of genes required for endometrial receptivity and a dampening of estrogen responsiveness. In the late proliferative phase, changes in immune function and NK cells predominate. The proliferative phase is not simply a uniform period of estrogen responsive endometrial growth that can be considered as a single experimental time point when evaluating endometrial development; rather the proliferative phase is complex with differing functions and patterns of gene expression.

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Section: Discussionmentioning

confidence: 99%

Global Gene Expression Profiling of Proliferative Phase Endometrium Reveals Distinct Functional Subdivisions

et al. 2012

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“…First-trimester decidua is characterized by dNK cell and macrophage dominance. In the second trimester, dominance is skewed toward CD4 Th cells, regulatory T cells, and a population of alternatively activated M2 macrophages (4,18). In this study, we describe a novel tissue resident neutrophil population appearing in the second trimester.…”

mentioning

confidence: 99%

“…We next assessed the potential peripheral blood origin of dNs and the role of CXCL8 in PMN differentiation. PMNs were isolated from blood collected from second-trimester women (weeks [15][16][17][18] and cultured with either serum-free control RPMI medium (SFM) or second-trimester DCMs 6 the neutralizing anti-CXCL8 Ab for 5 h. RNA was isolated, and expression of the angiogenic growth factors listed earlier along with levels of ICAM1 were quantified by real-time PCR (primer sequences for genes of interest are listed in Table II). The PMNs cultured with DCM had a significant increase in the relative expression of VEGFA (127-fold), CCL2 (545-fold), ARG1 (5-fold), and ICAM1 (5-fold) mRNA levels as compared with control medium cultured PMNs (p , 0.001).…”

Section: Cxcl8 Drives the Differentiation Of An Angiogenic Dn Populationmentioning

confidence: 99%

Identification of a Novel Neutrophil Population: Proangiogenic Granulocytes in Second-Trimester Human Decidua

Amsalem

Kwan

Hazan

et al. 2014

The Journal of Immunology

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101

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The maternal leukocytes of the first-trimester decidua play a fundamental role in implantation and early development of the fetus and placenta, yet little is known regarding the second-trimester decidual environment. Our multicolor flow cytometric analyses of human decidual leukocytes detected an elevation in tissue resident neutrophils in the second trimester. These cells in both human and murine samples were spatially restricted to decidua basalis. In comparison with peripheral blood neutrophils (PMNs), the decidual neutrophils expressed high levels of neutrophil activation markers and the angiogenesis-related proteins: vascular endothelial growth factor-A, Arginase-1, and CCL2, similarly shown in tumor-associated neutrophils. Functional in vitro assays showed that second-trimester human decidua conditioned medium stimulated transendothelial PMN invasion, upregulated VEGFA, ARG1, CCL2, and ICAM1 mRNA levels, and increased PMN-driven in vitro angiogenesis in a CXCL8-dependent manner. This study identified a novel neutrophil population with a physiological, angiogenic role in human decidua.

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“…Leucocytes may contribute to endometrial vascular remodelling by expressing and secreting angiogenic factors, or by simulating production of local factors required for vascular remodelling including VEGFA (recently reviewed by Dunk et al (2008)). Neutrophils have been hypothesised to have a specific role in Endometrial vascular remodelling endometrial angiogenesis.…”

Section: Vascular Endothelial Growth Factor-amentioning

confidence: 99%

Regulation of endometrial vascular remodelling: role of the vascular endothelial growth factor family and the angiopoietin–TIE signalling system

Girling¹,

Rogers²

2009

Reproduction

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Angiogenesis, lymphangiogenesis and vascular maturation occur on a regular, physiological basis in human endometrium. These processes form part of a continuum of vascular remodelling involving numerous regulatory factors. Key factors include vascular endothelial growth factor (VEGF)A, VEGFC and VEGFD, and their associated receptors VEGFR1, VEGFR2 and VEGFR3. A second group of vascular regulatory proteins belongs to the angiopoietin (ANG)-TIE system. Although members of the VEGF family and the ANG-TIE system are represented in the endometrium, our understanding of how these different molecules interact to regulate remodelling of the blood and lymphatic vasculature present in the endometrium is still limited. A review of the current information is provided.

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Promotion of Angiogenesis by Human Endometrial Lymphocytes

Cited by 27 publications

References 149 publications

Global Gene Expression Profiling of Proliferative Phase Endometrium Reveals Distinct Functional Subdivisions

Global Gene Expression Profiling of Proliferative Phase Endometrium Reveals Distinct Functional Subdivisions

Identification of a Novel Neutrophil Population: Proangiogenic Granulocytes in Second-Trimester Human Decidua

Regulation of endometrial vascular remodelling: role of the vascular endothelial growth factor family and the angiopoietin–TIE signalling system

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