Plasma from first trimester pre-symptomatic women who subsequently developed preeclampsia reduces extravillous trophoblast cells migration, a possible role of placental-derived particles

Placenta ◽  
2014 ◽  
Vol 35 (9) ◽  
pp. A83 ◽  
Author(s):  
Carlos Salomon ◽  
Sarah Yee ◽  
Suchismita Sarker ◽  
Katherin Scholz-Romero ◽  
Sebastian Illanes ◽  
...  
2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
J. Bolnick ◽  
L. Albitar ◽  
L. L. Laidler ◽  
R. Abdullah ◽  
K. K. Leslie

We identified a major peptide signaling target of EGF/EGFR pathway and explored the consequences of blocking or activating this pathway in the first trimester extravillous trophoblast cells, HTR-8/SVneo. A global analysis of protein phosphorylation was undertaken using novel technology (Kinexus Kinetworks) that utilizes SDS-polyacrylamide minigel electrophoresis and multi-lane immunoblotting to permit specific and semiquantitative detection of multiple phosphoproteins. Forty-seven protein phosphorylation sites were queried, and the results reported based on relative phosphorylation at each site. EGF- and Iressa-(gefitinib, ZD1839, an inhibitor of EGFR) treated HTR-8/SVneo cells were subjected to immunoblotting and flow cytometry to confirm the phosphoprotein screen and to assess the effects of EGF versus Iressa on cell cycle and apoptosis. EGFR mediates the phosphorylation of important signaling proteins, including PKBα/AKT. This pathway is likely to be central to EGFR-mediated trophoblast survival. Furthermore, EGF treatment induces proliferation and inhibits apoptosis, while Iressa induces apoptosis.


2010 ◽  
Vol 207 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Delphine Benaitreau ◽  
Esther Dos Santos ◽  
Marie-Christine Leneveu ◽  
Nadia Alfaidy ◽  
Jean-Jacques Feige ◽  
...  

Adiponectin is an adipokine with insulin-sensitizing, anti-inflammatory, anti-atherogenic, and anti-proliferative effects. The expression of specific adiponectin receptors in the placenta and in the endometrium suggests a role for this cytokine in placental development, but this role has not yet been elucidated. The invasion of trophoblast cells during the first trimester of pregnancy being crucial to placentation process, we have studied adiponectin effects on human trophoblast invasive capacities. We found that adiponectin stimulated human trophoblast cell migration in HTR-8/SVneo cells in a dose-independent manner. In addition, adiponectin also significantly enhanced invasion of HTR-8/SVneo cells and of human extravillous trophoblast from first trimester placenta. These pro-invasive effects of adiponectin in human trophoblasts seem to be mediated in part via increased matrix metalloproteinases (MMP2 and MMP9) activities and via repression of TIMP2 mRNA expression. Our results suggest that adiponectin could be a positive regulator of the early invasion process by modulating the MMP/TIMP balance. Moreover, these results provide an insight into the role of adiponectin in pathological conditions characterized by insufficient or excessive trophoblast invasion.


2018 ◽  
Author(s):  
Roser Vento-Tormo ◽  
Mirjana Efremova ◽  
Rachel A. Botting ◽  
Margherita Y. Turco ◽  
Miquel Vento-Tormo ◽  
...  

SummaryDuring the early weeks of human pregnancy, the fetal placenta implants into the uterine mucosa (decidua) where placental trophoblast cells intermingle and communicate with maternal cells. Here, we profile transcriptomes of ∼50,000 single cells from this unique microenvironment, sampling matched first trimester maternal blood and decidua, and fetal cells from the placenta itself. We define the cellular composition of human decidua, revealing five distinct subsets of decidual fibroblasts with differing growth factors and hormone production profiles, and show that fibroblast states define two distinct decidual layers. Among decidual NK cells, we resolve three subsets, each with a different immunomodulatory and chemokine profile. We develop a repository of ligand-receptor pairs (www.CellPhoneDB.org) and a statistical tool to predict the probability of cell-cell interactions via these pairs, highlighting specific interactions between decidual NK cells and invading fetal extravillous trophoblast cells, maternal immune and stromal cells. Our single cell atlas of the maternal-fetal interface reveals the cellular organization and interactions critical for placentation and reproductive success.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Danai Georgiadou ◽  
Souad Boussata ◽  
Willemijn H. M. Ranzijn ◽  
Leah E. A. Root ◽  
Sanne Hillenius ◽  
...  

AbstractPreeclampsia is a frequent gestational hypertensive disorder with equivocal pathophysiology. Knockout of peptide hormone ELABELA (ELA) has been shown to cause preeclampsia-like symptoms in mice. However, the role of ELA in human placentation and whether ELA is involved in the development of preeclampsia in humans is not yet known. In this study, we show that exogenous administration of ELA peptide is able to increase invasiveness of extravillous trophoblasts in vitro, is able to change outgrowth morphology and reduce trophoblast proliferation ex vivo, and that these effects are, at least in part, independent of signaling through the Apelin Receptor (APLNR). Moreover, we show that circulating levels of ELA are highly variable between women, correlate with BMI, but are significantly reduced in first trimester plasma of women with a healthy BMI later developing preeclampsia. We conclude that the large variability and BMI dependence of ELA levels in circulation make this peptide an unlikely candidate to function as a first trimester preeclampsia screening biomarker, while in the future administering ELA or a derivative might be considered as a potential preeclampsia treatment option as ELA is able to drive extravillous trophoblast differentiation.


2019 ◽  
Vol 514 (1) ◽  
pp. 58-63 ◽  
Author(s):  
Julieta Reppetti ◽  
Tomás Etcheverry ◽  
Matías N. Sierra ◽  
Alicia E. Damiano ◽  
Mariana Farina ◽  
...  

2009 ◽  
Vol 129 (11) ◽  
pp. 1423-1430
Author(s):  
Fumie HASHIMOTO ◽  
Asuka ONO ◽  
Kikumi MATSUOKA ◽  
Sadaki YOKOTA ◽  
Hiroyuki SEKI ◽  
...  

Endocrinology ◽  
2007 ◽  
Vol 149 (3) ◽  
pp. 1243-1251 ◽  
Author(s):  
Catalin Nicola ◽  
Andrei Chirpac ◽  
Peeyush K. Lala ◽  
Chandan Chakraborty

Prostaglandin (PG) E2 may regulate invasiveness of human placenta because we previously reported stimulation of migration of placental trophoblasts by PGE2 acting through PGE receptor (EP)-1 and activating calpain. RhoA GTPase and its important effector Rho kinase (ROCK) have also been previously shown to regulate trophoblast migration. Using immortalized HTR-8/SVneo trophoblast cells and first-trimester human chorionic villus explant cultures on matrigel, we further examined the role of RhoA/ROCK and MAPK (ERK1/2) pathways on PGE2-mediated stimulation of trophoblast migration. Migration of cytotrophoblasts was shown to be inhibited by treatment of the trophoblast cell line and chorionic villus explants with either cell-permeable C3 transferase or selective RhoA small interfering RNA. These inhibitions were significantly mitigated by the addition of PGE2, an EP1/EP3 agonist or an EP3/EP4 agonist, suggesting that RhoA plays an important role in trophoblast migration but may not be obligatory for PGE2 action. Treatment of HTR-8/SVneo cells with nonselective ROCK inhibitor Y27632 or ROCK small interfering RNAs inhibited migration of these cells, which could not be rescued with PGE2 or the other two EP agonists, suggesting the obligatory role of ROCK in PGE2-induced migratory response. Furthermore, U0126, an inhibitor of MAPK kinases MEK1 and MEK2, abrogated PGE2-induced migration of trophoblasts, and PGE2 or the other two EP agonists stimulated ERK1/2 activation in trophoblasts, which was not abrogated by pretreatment with C3 transferase, indicating that ERK signaling pathway is an efficient alternate pathway for RhoA in PGE2-mediated migration of trophoblasts. These results suggest that ROCK and ERK1/2 play more important roles than RhoA in PGE2-mediated migration stimulation of first-trimester trophoblasts.


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