213. Chemokines: key players at the maternal - fetal interface

2008 ◽  
Vol 20 (9) ◽  
pp. 13
Author(s):  
N. J. Hannan ◽  
L. A. Salamonsen
Keyword(s):  
Extracellular Matrix ◽  
Real Time ◽  
Extracellular Matrix Protein ◽  
Leukocyte Trafficking ◽  
Trophoblast Cells ◽  
Rt Pcr ◽  
Human Trophoblast ◽  
Decidual Cells ◽  
Trophoblast Migration ◽  
Maternal Fetal Interface

Establishment of pregnancy requires extensive communication at the maternal-fetal interface and involves a plethora of locally acting molecules, including the chemokines. Chemokines are multifunctional molecules initially described for roles in leukocyte trafficking, but since found to participate in many other processes such as differentiation and directed migration. Previously we have shown that the chemokines, CX3CL1 and CCL14, are abundant in human endometrial vasculature, leukocytes, epithelial and decidual cells at the time of implantation and that their receptors, CX3CR1 and CCR1, are present on invading human trophoblast. CX3CL1 and CCL14 directly promote human trophoblast migration. We hypothesised that these endometrial chemokines promote trophoblast migration by regulating adhesion molecules and extracellular matrix (ECM) components on the trophoblast, similar to mechanisms used in leukocyte trafficking. Trophoblast cells (AC1M-88) used previously, showed a marked increase in adhesion to fibronectin following treatment with CX3CL1 and CCL14. Alterations in trophoblast adhesion associated and ECM genes following chemokine stimulation were examined using pathway specific oligo-arrays and quantitative real-time RT–PCR. Over 30 transcripts were affected by CX3CL1 treatment and 15 were regulated by CCL14 treatment. Real-time RT–PCR confirmed significant changes in the mRNA transcripts of α-catenin (CTNNA1), extracellular matrix protein-1 (ECM1), osteopontin (SPP1), integrin α6 (ITGA6), matrix metalloproteinase-12 (MMP12) and integrin β5 (ITGB5) following chemokine treatment. Several of these molecules have previously been implicated in implantation. Immunohistochemistry confirmed the presence of integrin α6, SPP1 and ECM1 protein in first trimester human implantation sites. The temporal and spatial expression of chemokines, their receptors and adhesion related molecules at the maternal-fetal interface emphasises an important role in the controlled directional migration of trophoblast through the maternal decidua. For the first time this study demonstrates direct effects of CX3CL1 and CCL14 on trophoblast adhesion and ECM molecules suggesting mechanisms by which trophoblast cells migrate during early pregnancy.

scholarly journals The Cytokine Gene CXCL14 Restricts Human Trophoblast Cell Invasion by Suppressing Gelatinase Activity

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5596-5605 ◽  
Author(s):  
HaiBin Kuang ◽  
Qi Chen ◽  
Ying Zhang ◽  
Li Zhang ◽  
HongYing Peng ◽  
...  
Keyword(s):  
Trophoblast Cell ◽  
Trophoblast Invasion ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
Gelatinase Activity ◽  
Invasion And Migration ◽  
Human Pregnancy ◽  
Decidual Cells ◽  
And Migration ◽  
Maternal Fetal Interface

Abstract Well-controlled trophoblast invasion into uterine decidua is a critical process for the normal development of placenta, which is tightly regulated by various factors produced within the trophoblast-endometrial microenvironment. CXCL14 is involved in tumor growth and metastasis, and its expression in placenta is temporally regulated during pregnancy. However, the role of CXCL14 in trophoblast function during human pregnancy is not clear. In this study, by using RT-PCR through human pregnancy, we found that CXCL14 was selectively expressed at early but not late pregnancy. Immunostaining revealed that CXCL14 proteins were strongly expressed in villous cytotrophoblasts and moderately in decidualized stromal cells but very weakly in syncytiotrophoblasts and extravillous trophoblasts. The effect of CXCL14 on trophoblast invasion were examined by using human villous explants cultured on Matrigel and further proved by invasion and migration assay of primary trophoblast cells and trophoblast cell line HTR-8/SVneo. Our data showed that CXCL14 significantly inhibited outgrowth of villous explant in vitro; this effect is due to suppression of trophoblast invasion and migration through regulating matrix metalloproteinases activities, whereas the trophoblast proliferation was not affected. Moreover, because a receptor for CXCL14 has not been identified, we performed further cell-specific CXCL14 binding activities with regard to different cell types within the maternal-fetal interface. Our data revealed that CXCL14 could specifically bind to trophoblast cells but not decidual cells from the maternal-fetal interface. These results suggest that CXCL14 plays an important role in regulating trophoblast invasion through an autocrine/paracrine manner during early pregnancy.

Genetically engineered mice demonstrate that adenosine deaminase is essential for early postimplantation development

Development ◽  
1997 ◽  
Vol 124 (16) ◽  
pp. 3089-3097 ◽  
Author(s):  
M.R. Blackburn ◽  
T.B. Knudsen ◽  
R.E. Kellems
Keyword(s):  
Adenosine Deaminase ◽  
Genetically Modified ◽  
Genetically Engineered ◽  
Purine Metabolism ◽  
Trophoblast Cells ◽  
Relative Contribution ◽  
Decidual Cells ◽  
Genetically Engineered Mice ◽  
Essential Enzyme ◽  
Maternal Fetal Interface

Adenosine deaminase (ADA) is an essential enzyme of purine metabolism that is enriched at the maternal-fetal interface of mice throughout postimplantation development. During early postimplantation stages Ada is highly expressed in both maternally derived decidual cells and zygotically derived trophoblast cells. For the current study we utilized genetically modified mice to delineate the relative contribution and importance of decidual and trophoblast ADA at the maternal-fetal interface. In females genetically engineered to lack decidual ADA a striking pattern of expression was revealed in giant trophoblast cells that surround the early postimplantation embryo. Embryos within gestation sites lacking both decidual and trophoblast ADA died during the early postimplantation period, whereas expression in trophoblast cells alone was sufficient for survival through this period. Severe disturbances in purine metabolism were observed in gestation sites lacking decidual ADA, including the accumulation of the potentially toxic ADA substrates adenosine and 2′-deoxyadenosine. These experiments provide genetic evidence that Ada expression at the maternal-fetal interface is essential for early postimplantation development in mice.

205. Fractalkine, HCC-1 and MIP-1β promote human trophoblast migration

2005 ◽  
Vol 17 (9) ◽  
pp. 78
Author(s):  
N. J. Hannan ◽  
R. L. Jones ◽  
L. A. Salamonsen
Keyword(s):  
Stromal Cells ◽  
Chemokine Receptors ◽  
First Trimester ◽  
Conditioned Media ◽  
Receptor Expression ◽  
Extravillous Trophoblast ◽  
Vitro Assay ◽  
Human Trophoblast ◽  
Decidual Cells ◽  
Trophoblast Migration

Human embryo implantation is a complex process requiring the attachment of an activated blastocyst to receptive endometrial epithelium and subsequent trophoblast invasion throughout the first trimester of pregnancy. Chemokines, including fractalkine (FKN), MCP-3, HCC-1 and MIP-1β, are produced by human endometrial epithelial and decidual cells with maximal production around the time of implantation/early pregnancy.1,2 Chemokine and receptor expression was characterized in cell types at the human maternal–trophoblast interface. Highly abundant expression of chemokine receptors CX3CR1 and CCR1 was observed in first trimester placenta and in trophoblast cells.3 We hypothesized that CX3CR1 and CCR1 ligands (FKN, MCP-3, HCC-1 and MIP-1β) produced by endometrial epithelial and decidualised stromal cells at the time of implantation promote migration of human trophoblast. We aimed to localize specific chemokine receptors in human first trimester tissue, and to determine whether trophoblast migration could be stimulated by the endometrium and by chemokines. Cellular localisation of specific receptors was assessed by immunohistochemistry in human first trimester implantation sites. Using an in vitro assay, trophoblast migration was assessed in response to human endometrial epithelial (HEEC) and decidualised stromal cells (DESC) (serum-free) conditioned medium and to recombinant human FKN, MCP-3, HCC-1 and MIP-1β. CX3CR1 and CCR1 protein was localised to the vascular extravillous trophoblast (EVTs), but not to the invading interstitial EVTs, with weak staining on the syncytium. Significant migration of cells occurred in response to conditioned media from HEEC and DESC. FKN, MIP-1β and HCC-1, but not MCP-3 also promoted significant trophoblast migration. Neutralizing antibodies for FKN and MIP-1β but not MCP-3 significantly reduced migration to conditioned media, indicating that at least these two chemokines contributed to the effects. These data support a role for endometrial derived chemokines in promoting human trophoblast migration. (1)Jones et al. (2004). JCEM 89(12), 6155–6167.(2)Hannan et al. (2004). Reprod. Fert. Devel. 16(Suppl.), A225, p. 78.(3)Hannan et al. (2004). JCEM 89(12), 6119–6129.

scholarly journals Autocrine and Paracrine Mechanisms of Prostaglandin E2 Action on Trophoblast/Conceptus Cells through the Prostaglandin E2 Receptor (PTGER2) during Implantation

Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3864-3876 ◽  
Author(s):  
Agnieszka Waclawik ◽  
Piotr Kaczynski ◽  
Henry N. Jabbour
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Prostaglandin E2 ◽  
Mapk Signaling ◽  
Intercellular Adhesion Molecule ◽  
Pcr Analysis ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
Uterine Lumen ◽  
Estradiol 17Β

The conceptus and endometrium secrete large amounts of prostaglandin E2 (PGE2) into the porcine uterine lumen during the periimplantation period. We hypothesized that PGE2 acts on conceptus/trophoblast cells through auto- and paracrine mechanisms. Real-time RT-PCR analysis revealed that PGE2 receptor (PTGER)2 mRNA was 14-fold greater in conceptuses/trophoblasts on days 14–25 (implantation and early placentation period) vs preimplantation day 10–13 conceptuses (P < .05). Similarly, expression of PTGER2 protein increased during implantation. Conceptus expression of PTGER4 mRNA and protein did not differ on days 10–19. PGE2 stimulated PTGER2 mRNA expression in day 15 trophoblast cells through PTGER2 receptor signaling. PGE2 elevated aromatase expression and estradiol-17β secretion by trophoblast cells. Moreover, PGE2 and the PTGER2 agonist, butaprost, increased the adhesive capacity of both human HTR-8/SVneo trophoblast and primary porcine trophoblast cells to extracellular matrix. This PGE2-induced alteration in trophoblast cell adhesion to extracellular matrix was abolished by incubation of these cells with AH6809 (PTGER2 antagonist), ITGAVB3-directed tetrapeptide arg-gly-asp-ser or integrin ITGAVB3 antibody. PGE2 stimulated adhesion of porcine trophoblast cells via the estrogen receptor and MEK/MAPK signaling pathway. PGE2 induced phosphorylation of MAPK1/MAPK3 through PTGER2 and up-regulated expression of cell adhesion proteins such as focal adhesion kinase and intercellular adhesion molecule-1. Our study indicates that elevated PGE2 in the periimplantation uterine lumen stimulates conceptus PTGER2 expression, which in turn promotes trophoblast adhesion via integrins, and synthesis and secretion of the porcine embryonic signal estradiol-17β. Moreover, the mechanism through which PGE2 increases trophoblast adhesion is not species specific because it is PTGER2- and integrin-dependent in both porcine and human trophoblast cells.

Differentiation of human trophoblast cells in vitro stimulated by extracellular matrix

Placenta ◽  
1993 ◽  
Vol 14 ◽  
pp. 181-200
Author(s):  
Hans-Peter Hohn ◽  
Larry R. Boots ◽  
Hans-Werner Denker ◽  
Magnus Höök
Keyword(s):  
Extracellular Matrix ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
Human Trophoblast Cells

Role of extracellular matrix in regulation of type IV collagenase synthesis by human trophoblast cells and their malignant counterparts

Placenta ◽  
1993 ◽  
Vol 14 ◽  
pp. 201-210
Author(s):  
Hervé Emonard ◽  
Maryam Aghayan ◽  
Monique Smet ◽  
Jean-Pierre Schaaps ◽  
Jean-Alexis Grimaud ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Trophoblast Cells ◽  
Type Iv Collagenase ◽  
Human Trophoblast ◽  
Type Iv ◽  
Human Trophoblast Cells

scholarly journals 254.Interleukin-11 enhances endometrial stromal cell decidualisation via activation and inhibition of target genes

2004 ◽  
Vol 16 (9) ◽  
pp. 254
Author(s):  
C. A. White ◽  
E. Dimitriadis ◽  
A. Sharkey ◽  
C. J. Stoikos ◽  
L. A. Salamonsen
Keyword(s):  
Gene Expression ◽  
Real Time ◽  
Stromal Cells ◽  
Target Genes ◽  
Fold Change ◽  
Rt Pcr ◽  
Endometrial Stromal Cells ◽  
Cytoplasmic Staining ◽  
Decidual Cells ◽  
Custom Made

Differentiation of endometrial stromal cells into decidual cells is essential for successful embryo implantation. Interleukin (IL)-11 signalling is required for decidualisation in the mouse (1,2) and the expression pattern of IL-11 and its receptors during the menstrual cycle suggests a role for IL-11 in human decidualisation (3). Exogenous IL-11 has been shown to enhance hormone-induced decidualisation of human endometrial stromal cells in culture (4). This study aimed to determine the effects of IL-11 on downstream gene expression in endometrial stromal cells following 12 days of progesterone-induced decidualisation, and to examine the expression and functional significance of IL-11 target genes during this process. Stromal cells isolated from endometrial biopsies (n = 6) were decidualised with 17β-oestradiol and medroxyprogesterone acetate (EP) or EP with 100 ng/mL recombinant human IL-11. Medium was changed every 48 h, and total RNA extracted on Day 12 for gene expression analysis using custom-made 15K cDNA microarrays. Quantitative real-time RT-PCR was performed on the same samples to confirm gene expression levels. In subsequent experiments (n = 2), cells were cytocentrifuged onto glass slides for immunocytochemistry using specific antibodies. Microarray analysis revealed 16 upregulated and 11 downregulated cDNAs in EP + IL-11 compared to EP treated cells. Among these were IL-1β (6.1-fold upregulated) and insulin-like growth factor binding protein (IGFBP)-5 (3.6-fold downregulated). Using real-time RT-PCR, IL-11 was confirmed to increase IL-1β (fold change 1.3–107.1) and decrease IGFBP-5 (fold change 2.8–469.0) transcript abundance in 6 patients. Immunolocalisation of IL-1β in EP and EP + IL-11 treated cells revealed more intense vesicular cytoplasmic staining with IL-11 treatment, while staining intensity for IGFBP-5 was not affected. Interactions between IL-11 and its downstream targets IL-1β and IGFBP-5 are likely to have functional importance in early pregnancy, and may provide novel targets for the manipulation of human fertility. (1) Robb L, Li R, Hartley L, Nandurkar HH, Koentgen F, Begley CG (1998) Nat. Med. 4, 303–308. (2) Bilinski P, Roopenian D, Gossler A (1998) Gene Dev. 12, 2234–2243. (3) Dimitriadis E, Salamonsen LA, Robb L (2000) Mol. Hum. Reprod. 6, 907–914. (4) Dimitriadis E, Robb L, Salamonsen LA (2002) Mol. Hum. Reprod. 8, 636–643.

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