scholarly journals MTA3 Regulates Extravillous Trophoblast Invasion Through NuRD Complex

2017 ◽  
Vol 4 (1) ◽  
pp. 17-27 ◽  
Author(s):  
Ying Chen ◽  
◽  
Sok Kean Khoo ◽  
Richard Leach ◽  
Kai Wang
Keyword(s):  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Nurd Complex

scholarly journals Low chorionic villous succinate accumulation associates with recurrent spontaneous abortion risk

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiao-Hui Wang ◽  
Sha Xu ◽  
Xiang-Yu Zhou ◽  
Rui Zhao ◽  
Yan Lin ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Embryo Implantation ◽  
Underlying Mechanism ◽  
Recurrent Spontaneous Abortion ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Iron Sulfur ◽  
Succinate Dehydrogenase Complex ◽  
Extravillous Trophoblasts ◽  
Control Study

AbstractDysregulated extravillous trophoblast invasion and proliferation are known to increase the risk of recurrent spontaneous abortion (RSA); however, the underlying mechanism remains unclear. Herein, in our retrospective observational case-control study we show that villous samples from RSA patients, compared to healthy controls, display reduced succinate dehydrogenase complex iron sulfur subunit (SDHB) DNA methylation, elevated SDHB expression, and reduced succinate levels, indicating that low succinate levels correlate with RSA. Moreover, we find high succinate levels in early pregnant women are correlated with successful embryo implantation. SDHB promoter methylation recruited MBD1 and excluded c-Fos, inactivating SDHB expression and causing intracellular succinate accumulation which mimicked hypoxia in extravillous trophoblasts cell lines JEG3 and HTR8 via the PHD2-VHL-HIF-1α pathway; however, low succinate levels reversed this effect and increased the risk of abortion in mouse model. This study reveals that abnormal metabolite levels inhibit extravillous trophoblast function and highlights an approach for RSA intervention.

Roles of TGF-β Superfamily Proteins in Extravillous Trophoblast Invasion

2021 ◽  
Vol 32 (3) ◽  
pp. 170-189
Author(s):  
Yan Li ◽  
Junhao Yan ◽  
Hsun-Ming Chang ◽  
Zi-Jiang Chen ◽  
Peter C.K. Leung
Keyword(s):  
Extravillous Trophoblast ◽  
Trophoblast Invasion

scholarly journals Silencing SEC5 inhibits trophoblast invasion via integrin/Ca2+ signaling

Reproduction ◽  
2020 ◽  
Vol 159 (1) ◽  
pp. 59-71
Author(s):  
Wen-Wen Gu ◽  
Long Yang ◽  
Xing-Xing Zhen ◽  
Yan Gu ◽  
Hua Xu ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
First Trimester ◽  
Cytosolic Calcium ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Migration And Invasion ◽  
Third Trimester ◽  
Imaging Results ◽  
Fetal Bovine ◽  
And Migration

The invasion of maternal decidua by extravillous trophoblast (EVT) is essential for the establishment and maintenance of pregnancy, and abnormal trophoblast invasion could lead to placenta-associated pathologies including early pregnancy loss and preeclampsia. SEC5, a component of the exocyst complex, plays important roles in cell survival and migration, but its role in early pregnancy has not been reported. Thus, the present study was performed to explore the functions of SEC5 in trophoblast cells. The results showed that SEC5 expression in human placental villi at first trimester was significantly higher than it was at the third trimester, and it was abundantly localized in the cytotrophoblast (CTB) and the trophoblastic column. SEC5 knockdown was accompanied by reduced migration and invasion in HTR-8/SVneo cells. In addition, the expression and plasma membrane distribution of integrin β1 was also decreased. Furthermore, shRNA-mediated knockdown of SEC5 inhibited the outgrowth of first trimester placental explants. SEC5 and InsP3R were colocalized in the cytoplasm of HTR-8/SVneo cells, and the cell-permeant calcium chelator BAPTA-AM could significantly inhibit HTR-8/SVneo cell invasion. The Ca2+ imaging results showed that the 10% fetal bovine serum-stimulated cytosolic calcium concentration ([Ca2+]c) was not only reduced by downregulated SEC5 but also was blocked by the InsP3R inhibitor. Furthermore, either the [Ca2+]c was buffered by BAPTA-AM or the knockdown of SEC5 disrupted HTR-8/SVneo cell F-actin stress fibers and caused cytoskeleton derangement. Taken together, our results suggest that SEC5 might be involved in regulating trophoblast cell migration and invasion through the integrin/Ca2+ signal pathway to induce cytoskeletal rearrangement.

Impaired Sphingosine-1-Phosphate Synthesis Induces Preeclampsia by Deactivating Trophoblastic YAP (Yes-Associated Protein) Through S1PR2 (Sphingosine-1-Phosphate Receptor-2)-Induced Actin Polymerizations

Hypertension ◽  
2021 ◽  
Author(s):  
Jiujiang Liao ◽  
Yangxi Zheng ◽  
Mingyu Hu ◽  
Ping Xu ◽  
Li Lin ◽  
...  
Keyword(s):  
Actin Polymerization ◽  
Sphingosine Kinase ◽  
Actin Dynamics ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Hippo Signaling ◽  
Dependent Manner ◽  
Sphingosine Kinase 1 ◽  
Sphingosine 1 Phosphate

Incomplete spiral artery remodeling, caused by impaired extravillous trophoblast invasion, is a fundamental pathogenic process associated with malplacentation and the development of preeclampsia. Nevertheless, the mechanisms controlling this regulation of trophoblast invasion are largely unknown. We report that sphingosine-1-phosphate synthesis and expression is abundant in healthy trophoblast, whereas in pregnancies complicated by preeclampsia the placentae are associated with reduced sphingosine-1-phosphate and lower SPHK1 (sphingosine kinase 1) expression and activity. In vivo inhibition of sphingosine kinase 1 activity during placentation in pregnant mice led to decreased placental sphingosine-1-phosphate production and defective placentation, resulting in a preeclampsia phenotype. Moreover, sphingosine-1-phosphate increased HTR8/SVneo (immortalized trophoblast cells) cell invasion in a Hippo-signaling–dependent transcriptional coactivator YAP (Yes-associated protein) dependent manner, which is activated by S1PR2 (sphingosine-1-phosphate receptor-2) and downstream RhoA/ROCK induced actin polymerization. Mutation-based YAP-5SA demonstrated that sphingosine-1-phosphate activation of YAP could be either dependent or independent of Hippo signaling. Together, these findings suggest a novel pathogenic pathway of preeclampsia via disrupted sphingosine-1-phosphate metabolism and signaling-induced, interrupted actin dynamics and YAP deactivation; this may lead to potential novel intervention targets for the prevention and management of preeclampsia.

scholarly journals A 3-dimensional microfluidic platform for modeling human extravillous trophoblast invasion and toxicological screening

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Yong Pu ◽  
Jeremy Gingrich ◽  
Almudena Veiga-Lopez
Keyword(s):  
Cell Invasion ◽  
Dynamic Environment ◽  
Cell Interaction ◽  
Microfluidic System ◽  
Trophoblast Cell ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Toxicological Screening ◽  
Microfluidic Platform ◽  
3 Dimensional

A novel 3D microfluidic system for placenta trophoblast cell invasion and cell-to-cell interaction studies under dynamic environment conditions.

scholarly journals EGF-induced trophoblast secretion of MMP-9 and TIMP-1 involves activation of both PI3K and MAPK signalling pathways

Reproduction ◽  
2004 ◽  
Vol 128 (3) ◽  
pp. 355-363 ◽  
Author(s):  
Q Qiu ◽  
M Yang ◽  
B K Tsang ◽  
A Gruslin
Keyword(s):  
Tissue Inhibitor Of Metalloproteinase ◽  
Mitogen Activated Protein Kinase ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Signalling Pathways ◽  
Placental Development ◽  
Mapk Pathways ◽  
Erk Phosphorylation ◽  
Gene And Protein Expression ◽  
Extravillous Trophoblasts

Epidermal growth factor (EGF) is present in the maternal-fetal environment and has an important role in placental development. Matrix metalloproteinase-9 (MMP-9) expression/activation is a pre-requisite in extravillous trophoblast invasion. Whereas EGF up-regulates MMP-9 activity in a variety of cell types, there is no direct evidence for the stimulation of MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) secretion by EGF in extravillous trophoblasts. In addition, the signalling pathways involved in this regulation are not clear. In the present study, we have examined the possible involvement of the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in the regulation of the MMP-9/TIMP-1 system by EGFin vitro. We used a well-established invasive extravillous trophoblast cell line (HTR8/Svneo) and measured gene and protein expression by semi-quantitative RT-PCR and western analysis respectively. MMP activity was determined by zymography. We showed for the first time that EGF activated both PI3K/Akt and MAPK/extracellular-signal regulated kinase (ERK) signalling in HTR8/SVneo, and increased both MMP-9 and TIMP-1 mRNAs and protein concentrations. Interfering with either signalling pathway via PI3K inhibitor LY294002 or MEK inhibitor U0126 in EGF-stimulated HTR8/SVneo cells blocked the induction of MMP-9 and TIMP-1. LY294002 inhibited Akt phosphorylation, but had no effect on ERK phosphorylation; U0126 suppressed ERK phosphorylation without interfering with the phosphorylation of Akt. In addition, expression of constitutively active Akt (Myr-Akt1, Myr-Akt2, Myr-Akt3) was not sufficient to induce proMMP-9 and TIMP-1 secretion. Our results suggest that the activation of both PI3K and MAPK pathways in extravillous trophoblasts is necessary for the up-regulation of MMP-9 and TIMP-1 expression by EGF.

Extravillous trophoblast invasion accelerated by WNT3A, 5A, and 10B via CD44

2019 ◽  
pp. 1-9 ◽  
Author(s):  
Hironori Takahashi ◽  
Manabu Ogoyama ◽  
Shiho Nagayama ◽  
Hirotada Suzuki ◽  
Akihide Ohkuchi ◽  
...  
Keyword(s):  
Extravillous Trophoblast ◽  
Trophoblast Invasion
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