scholarly journals Tubulin detyrosination promotes human trophoblast syncytium formation

2019 ◽  
Vol 11 (11) ◽  
pp. 967-978 ◽  
Author(s):  
Rui Wang ◽  
Ruoxuan Yu ◽  
Cheng Zhu ◽  
Hai-Yan Lin ◽  
Xiaoyin Lu ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Syncytium Formation ◽  
First Trimester ◽  
Trophoblast Cells ◽  
Placental Development ◽  
Human Trophoblast ◽  
Junction Protein ◽  
Elevated Expression ◽  
Surface Localization ◽  
Cytotrophoblast Cells

Abstract Human trophoblast syncytialization is one of the most important yet least understood events during placental development. In this study, we found that detyrosinated α-tubulin (detyr-α-tub), which is negatively regulated by tubulin tyrosine ligase (TTL), was elevated during human placental cytotrophoblast fusion. Correspondingly, relatively high expression of TTL protein was observed in first-trimester human placental cytotrophoblast cells, but fusing trophoblast cells exhibited much lower levels of TTL. Notably, fusion of preeclamptic cytotrophoblast cells was compromised but could be partially rescued by knockdown of TTL levels. Mechanistically, chronic downregulation of TTL in trophoblast cells resulted in significantly elevated expression of detyr-α-tub. Restoration of detyr-α-tub thus contributed to the cell surface localization of the fusogenic protein Syncytin-2 and the gap junction protein Connexin 43 (Cx43), which in turn promoted successful fusion between trophoblast cells. Taken together, the results suggest that tubulin detyrosination plays an essential role in human trophoblast fusogenic protein aggregation and syncytialization. Insufficient tubulin detyrosination leads to defects in syncytialization and potentially to the onset of preeclampsia.

110. EFFECTS OF cAMP AND SERUM ON HUMAN TROPHOBLAST CELL VIABILITY AND DIFFERENTIATION

2009 ◽  
Vol 21 (9) ◽  
pp. 29
Author(s):  
Y. Chen ◽  
M. Allars ◽  
C. Abou-Seif ◽  
R. C. Nicholson
Keyword(s):  
Cell Viability ◽  
Syncytium Formation ◽  
Culture Conditions ◽  
Trophoblast Cell ◽  
Bewo Cell ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
Serum Free ◽  
Bewo Cells ◽  
Free Media

The formation of syncytium is a pivotal event for trophoblast cells to interact with the placental bed. While cAMP is regarded as an inducer of syncytialisation, the affect of different culture conditions on this cAMP effect has not been explored. Therefore, the effects of cAMP on cell differentiation and viability in the presence or absence of serum were investigated in the human choriocarcinoma cell lines, BeWo and JEG-3. We observed that in the absence of cAMP, BeWo cells grew best in media containing 10% FCS, followed by media containing charcoal-stripped 10% FCS (10%CCS), and less well in serum-free media. In the presence of cAMP ( 0.25~1.5 mM ), our observations suggest different cellular programmes may be in play. Treatment of BeWo cells with 0.75 mM cAMP for 24h and 48h, in the absence of serum, increased cell viability (MTT assay) by 25.1% and 46.1% respectively, compared to the control cells. Interestingly, this cAMP effect on cell viability was not observed in the JEG-3 cell line. In contrast, BeWo cell viability was decreased by 49.5% and 25.2%, and by 27.5% and 31.1% in JEG-3 cells, when the cAMP stimulated cells were cultured for 48h in 10% CCS and 10% FCS media, respectively. In addition, we observed a change in BeWo, but not JEG-3, cell morphology to a spindle-like shape with pseudopodia when cAMP stimulated cells were cultured in media containing 10% CCS or 10% FCS for greater than 24h. Since the process of syncytialisation may involve apoptotic events, we speculate that the different effects of cAMP on cell viability in trophoblast cells may be related to syncytialising factors contained in serum media. Further study will clarify whether serum promotes syncytium formation, while the lack of serum based factors could switch the cellular programme from one of syncytialisation toward a more proliferative type.

scholarly journals Kidney-Replenishing Herb Induces SOCS-3 Expression via ERK/MAPK Pathway and Improves Growth of the First-Trimester Human Trophoblast Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-12
Author(s):  
Chang-ying Xing ◽  
De-xiang Zhang ◽  
Sui-qi Gui ◽  
Min-fang Tao
Keyword(s):  
Mapk Pathway ◽  
Recurrent Miscarriage ◽  
First Trimester ◽  
Mek Inhibitor ◽  
Biological Functions ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
Mitogen Activated Protein ◽  
Human Trophoblast Cells

Kidney-replenishing herb is a traditional medicine formula in China which has been widely used for clinical treatment of recurrent miscarriage. Our previous study showed that Kidney-replenishing herb could promote proliferation and inhibit apoptosis of the human first-trimester trophoblasts. In the present study, we further explored the potential mechanism and signal pathway of Kidney-replenishing herb on human trophoblast cells. Our research showed that Kidney-replenishing herb stimulated proliferation and reduced apoptosis of human trophoblast cells in vitro, and this appeared to be positive correlation with SOCS-3 transcription, suggesting that Kidney-replenishing herb regulated biological functions of human trophoblast cells by inducing SCOS-3 expression. Furthermore, the Kidney-replenishing herb treatment stimulated the phosphorylation of ERK1/2, and blocking the signaling pathway by mitogen-activated protein MAPK (MEK) inhibitor, U0126, inhibited Kidney-replenishing herb-induced SOCS-3 transcription, depressed proliferation, and promoted apoptosis of human trophoblasts. Kidney-replenishing herbs still induced ERK1/2 phosphorylation after SOCS-3 siRNA silence. Overexpression of SOCS-3 stimulated the proliferation of trophoblast. These findings suggest that SOCS-3 expression is induced by Kidney-replenishing herbs via activation of MAPK pathways, and this may possibly be involved in promoting human trophoblast cells growth which is contributed to embryo development.

scholarly journals Involvement of nephrin in human placental trophoblast syncytialization

Reproduction ◽  
2015 ◽  
Vol 149 (4) ◽  
pp. 339-346 ◽  
Author(s):  
Yue Li ◽  
Ru Zheng ◽  
Rui Wang ◽  
Xiaoyin Lu ◽  
Cheng Zhu ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Connexin 43 ◽  
Transmembrane Protein ◽  
First Trimester ◽  
Trophoblast Cell ◽  
Term Pregnancy ◽  
Fusion Model ◽  
Placental Development ◽  
Functional Conservation ◽  
Ig Superfamily

The placenta has numerous functions, such as transporting oxygen and nutrients and building the immune tolerance of the fetus. Cell fusion is an essential process for placental development and maturation. In human placental development, mononucleated cytotrophoblast (CTB) cells can fuse to form a multinucleated syncytiotrophoblast (STB), which is the outermost layer of the placenta. Nephrin is a transmembrane protein that belongs to the Ig superfamily. Previous studies have shown that nephrin contributes to the fusion of myoblasts into myotubes in zebrafish and mice, presenting a functional conservation with its Drosophila ortholog sticks and stones. However, whether nephrin is involved in trophoblast syncytialization remains unclear. In this study, we report that nephrin was localized predominantly in the CTB cells and STB of human placenta villi from first trimester to term pregnancy. Using a spontaneous fusion model of primary CTB cells, the expression of nephrin was found to be increased during trophoblast cell fusion. Moreover, the spontaneous syncytialization and the expression of syncytin 2, connexin 43, and human chorionic gonadotropin beta were significantly inhibited by nephrin-specific siRNAs. The above results demonstrate that nephrin plays an important role in trophoblast syncytialization.

Immunoregulatory activity in supernatants from cultures of normal human trophoblast cells of the first trimester

1989 ◽  
Vol 161 (2) ◽  
pp. 446-453 ◽  
Author(s):  
Mrinal K. Sanyal ◽  
Charles J. Brami ◽  
Paul Bischof ◽  
Edwina Simmons ◽  
Eytan R. Barnea ◽  
...  
Keyword(s):  
First Trimester ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
Normal Human ◽  
Human Trophoblast Cells

scholarly journals Effects of adiponectin on human trophoblast invasion

2010 ◽  
Vol 207 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Delphine Benaitreau ◽  
Esther Dos Santos ◽  
Marie-Christine Leneveu ◽  
Nadia Alfaidy ◽  
Jean-Jacques Feige ◽  
...  
Keyword(s):  
First Trimester ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Placental Development ◽  
Independent Manner ◽  
Human Trophoblast ◽  
Pathological Conditions ◽  
First Trimester Of Pregnancy ◽  
Insight Into

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.

Effects of hypoxia on heme oxygenase expression in human chorionic villi explants and immortalized trophoblast cells

2003 ◽  
Vol 284 (3) ◽  
pp. H853-H858 ◽  
Author(s):  
S. D. Appleton ◽  
G. S. Marks ◽  
K. Nakatsu ◽  
J. F. Brien ◽  
G. N. Smith ◽  
...  
Keyword(s):  
Protein Expression ◽  
Protein Content ◽  
Heme Oxygenase ◽  
Protein Function ◽  
Cell Types ◽  
First Trimester ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
Chorionic Villi ◽  
Enzymatic Function

Although hypoxia induces heme oxygenase (HO)-1 protein and mRNA expression in many cell types, hypoxia has also been shown to decrease HO-1 mRNA and protein expression. We tested the hypothesis that 24-h preexposure to hypoxia in human placental preparations suppresses HO protein expression and enzymatic function. Immortalized HTR-8/SVneo first-trimester trophoblast cells and explants of normal human chorionic villi (CV) from term placentas were cultured for 24 h in 1%, 5%, or 20% O2. HO protein levels were determined by Western blot analysis, and microsomal HO activity was measured. HO-2 protein content was decreased by 17% and 5% in human trophoblast cells after 24-h exposure to 1% and 5% O2, respectively, versus 20% O2. In contrast, HO-2 protein content in CV explants was unaffected by changes in oxygenation. HO-1 protein content, which was barely detectable in both biological systems, was not affected by changes in oxygenation. Similarly, HO enzymatic activity was unchanged in both preparations after 24-h exposure to 1%, 5%, or 20% O2. The above data do not support the hypothesis that hypoxia in the human placenta suppresses both HO protein content and HO protein function. The present observations reinforce the necessity to determine both HO protein expression and function.

Connexin Expression Patterns in Human Trophoblast Cells during Placental Development

Placenta ◽  
1999 ◽  
Vol 20 (8) ◽  
pp. 627-638 ◽  
Author(s):  
E Winterhager ◽  
C Von Ostau ◽  
M Gerke ◽  
R Gruemmer ◽  
O Traub ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Trophoblast Cells ◽  
Placental Development ◽  
Human Trophoblast ◽  
Connexin Expression ◽  
Human Trophoblast Cells

scholarly journals Oxidative Stress Alters miRNA and Gene Expression Profiles in Villous First Trimester Trophoblasts

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Courtney E. Cross ◽  
Mai F. Tolba ◽  
Catherine M. Rondelli ◽  
Meixiang Xu ◽  
Sherif Z. Abdel-Rahman
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Mrna Expression ◽  
Expression Profiles ◽  
First Trimester ◽  
Mirna Profile ◽  
Trophoblast Cells ◽  
Placental Development ◽  
Short Term ◽  
Short Term Exposure

The relationship between oxidative stress and miRNA changes in placenta as a potential mechanism involved in preeclampsia (PE) is not fully elucidated. We investigated the impact of oxidative stress on miRNAs and mRNA expression profiles of genes associated with PE in villous 3A first trimester trophoblast cells exposed to H2O2at 12 different concentrations (0-1 mM) for 0.5, 4, 24, and 48 h. Cytotoxicity, determined using the SRB assay, was used to calculate the IC50of H2O2. RNA was extracted after 4 h exposure to H2O2for miRNA and gene expression profiling. H2O2exerted a concentration- and time-dependent cytotoxicity on 3A trophoblast cells. Short-term exposure of 3A cells to low concentration of H2O2(5% of IC50) significantly altered miRNA profile as evidenced by significant changes in 195 out of 595 evaluable miRNAs. Tool for annotations of microRNAs (TAM) analysis indicated that these altered miRNAs fall into 43 clusters and 34 families, with 41 functions identified. Exposure to H2O2altered mRNA expression of 22 out of 84 key genes involved in dysregulation of placental development. In conclusion, short-term exposure of villous first trimester trophoblasts to low concentrations of H2O2significantly alters miRNA profile and expression of genes implicated in placental development.

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