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.

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.

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 The Downregulation of Placental Lumican Promotes the Progression of Preeclampsia

2021 ◽  
Author(s):  
Chao Liu ◽  
Yulian Hu ◽  
Zhongying Wang ◽  
Hua Pan ◽  
Yan Ren ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Line ◽  
Control Group ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
P53 Expression ◽  
Fluorescence Quantitative Pcr ◽  
And Migration ◽  
Negative Controls ◽  
The Impact

AbstractMultiple pieces of evidence illustrate that impaired trophoblast function results in preeclampsia (PE), and migration/invasion of human trophoblast cells is stringently regulated by extracellular matrix (ECM) components. Many studies have indicated abnormal expressions of placental ECM components are associated with preeclampsia. However, the change and influence of lumican, a vital member of extracellular matrix (ECM) molecules, on trophoblast cells during preeclampsia remain unclear. This study examines the possibility that the roles of lumican in trophoblast cells contribute to PE. To address this issue, the expression of lumican in human placental tissues was observed using immunohistochemistry, fluorescence quantitative PCR, and Western blot technology. After the HTR-8/SVneo cell line was transfected with pcDNA3.1-human lumican, pGPU6-human lumican shRNA, and their negative controls, the impact of lumican on the HTR-8/SVneo cell line was investigated. Lumican was expressed in human placental tissues. Compared with the control group, its expression was significantly lower in PE placentas. Lumican downregulation inhibited cell proliferation significantly and reduced Bcl-2 expression, but increased P53 expression. These results indicate that the downregulation of placental lumican may drive PE development via promoting the downregulation of Bcl-2 expression and upregulation of P53.

scholarly journals Small Guanosine Triphospatase RhoA and Rho-Associated Kinase as Regulators of Trophoblast Migration

2002 ◽  
Vol 87 (12) ◽  
pp. 5808-5816 ◽  
Author(s):  
Shigetatsu Shiokawa ◽  
Mitsutoshi Iwashita ◽  
Yoshihiro Akimoto ◽  
Shinya Nagamatsu ◽  
Ken Sakai ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Stress Fibers ◽  
Extravillous Trophoblast ◽  
Dependent Manner ◽  
Focal Contact ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
Trophoblast Migration ◽  
Human Trophoblast Cells ◽  
Actin Stress Fibers

Abstract The small guanosine triphosphatase Rho controls cell adhesion and motility through reorganization of the actin cyto-skeleton and regulation of actomyosin contractility. Among the putative target molecules of Rho, a Rho-associated coiled coil-forming protein kinase (ROCK) is thought to participate in Rho-mediated cell adhesion and motility. In the present study, we explored the expression and function of RhoA and ROCK in human trophoblast cells. The colocalization of RhoA, cytokeratin 8/18, and cytokeratin 7 in some cells located in the decidual stromal region indicated that extravillous trophoblast cells expressed RhoA. In double staining for RhoA and ROCK in human chorionic villi, RhoA staining was strongly positive in the cytoplasm of cytotrophoblasts, whereas ROCK stained in the cytoplasm of cytotrophoblasts and syncytiotrophoblasts. Both RhoA and ROCK were stained in cytoplasma of cultured human cytotrophoblast. Cultured human trophoblast cells contained actin stress fibers that were lost after treatment with C3, an exoenzyme produced by Clostridium botulinum. Y-27632, a selective ROCK inhibitor, suppressed RhoA-induced formation of actin stress fibers and formation of focal contact in trophoblast cells. The trophoblast reacquired actin stress fibers and focal contact after withdrawal of Y-27632. Cultured human cytotrophoblast cells from 7–9 wk of gestation migrated into a fibronectin-coated membrane. Both C3 exoenzyme and Y-27632 inhibited cytotrophoblast migration in a dose-dependent manner. In conclusion, cyto-trophoblasts express RhoA and ROCK in their cytoplasm, and RhoA-ROCK is involved in their assembly of actin stress fibers. Suppression of RhoA-ROCK reduces trophoblast migration. These findings suggest that RhoA-ROCK signaling is a key regulator of trophoblast cell migration.

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