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.

scholarly journals Human Uterine Decidual NK Cells in Women with a History of Early Pregnancy Enhance Angiogenesis and Trophoblast Invasion

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Ningyi Jia ◽  
Jian Li
Keyword(s):  
Early Pregnancy ◽  
Mrna Level ◽  
Trophoblast Invasion ◽  
Migration And Invasion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Mrna Levels ◽  
History Of ◽  
And Migration ◽  
Primiparous Women

Objective. The present study aimed to identify changes in decidual natural killer (dNK) cells and related cytokines in women who have undergone induced abortions (IAs). The effects of dNK cells on subsequent pregnancies remain unknown. Accordingly, we sought to investigate whether a history of early pregnancy can change dNK cells and facilitate their role in the regulation of angiogenesis and trophoblast invasion. Materials and Methods. dNK cells were obtained from primiparous women who had undergone IA(s) prior to this study and primiparous women who had never been pregnant before this IA (control). Real-time polymerase chain reaction (PCR) was used to measure the mRNA levels of IFN-γ, IP-10, VEGF, and PLGF in dNK cells. The levels of these cytokines were quantified using the enzyme-linked immunosorbent assay. HUVEC and HTR-8/SVneo cells were used to evaluate the angiogenesis, migration, and invasion activities influenced by dNK cells. Results. In dNK cells, the mRNA level of IFN-γ was higher in the control group than that in the IA group. The secretion of IP-10 and VEGF was higher in the IA group compared to the control group. After coculturing with the dNK supernatant, the HTR-8/SVneo cells exhibited better invasiveness and migration in the IA group than those in the control group. Angiogenesis assay demonstrated that dNK cells from IA group might help HUVEC attain better tube formation ability. Conclusion. The findings of this study suggest that a history of early pregnancy has an impact on dNK cells. These trained dNK cells can regulate angiogenesis and trophoblast invasion and migration by promoting the production of certain cytokines.

MNSFβ Promotes the Proliferation and Migration of Human Extravillous Trophoblast Cells and the Villus Expression Level of MNSFβ Is Decreased in Recurrent Miscarriage Patients

2020 ◽  
Vol 86 (1-2) ◽  
pp. 27-39
Author(s):  
Nan Wang ◽  
Qian Yang ◽  
Yan Gu ◽  
Xingxing Zhen ◽  
Yan Shi ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Recurrent Miscarriage ◽  
First Trimester ◽  
Expression Level ◽  
Extravillous Trophoblast ◽  
Placental Villus ◽  
Expression Levels ◽  
Placental Villi ◽  
And Migration ◽  
Proliferation And Migration

<b><i>Aims:</i></b> The invasion of extravillous trophoblast (EVT) cells into maternal decidua is essential for the establishment and maintenance of pregnancy. Derangement of EVT cell invasion might cause pregnancy complications including recurrent miscarriage (RM). We previously reported that deficiency of monoclonal nonspecific suppressor factor beta (MNSFβ) led to the early pregnancy failure in mice and the decidual MNSFβ expression level in RM patients was significantly decreased, but the underlying molecular mechanism of the role that MNSFβ played at the maternal-fetal interface remains unclear. Thus, in the present study, we determined effects of downregulated MNSFβ expression on human EVT cell activities. <b><i>Methods:</i></b> The MNSFβ expression in first-trimester human decidual and placental villus tissues was detected, respectively, by immunofluorescence or immunohistochemical analyses. The MNSFβ expression level in the immortalized first-trimester human EVT cell line HTR8/SVneo was downregulated by transfecting the small interfering RNA against MNSFβ and upregulated by transfecting the recombinant pDsRed-MNSFβ plasmids. The proliferation, migration, invasion, and apoptosis activities of HTR8/SVneo cells were, respectively, determined by cytometry assay, scratch test, transwell assay, and FITC/PI staining. The expression levels of P53, RhoA, Bcl-2, Bax, and MMP-9 in HTR8/SVneo cells, as well as the expression levels of MNSFβ and RhoA in placental villi of RM patients and physically normal pregnant women (NP), were examined by Western blot analysis. <b><i>Results:</i></b> MNSFβ protein signals were observed in first-trimester human villus and extravillous trophoblast cells. The downregulated MNSFβ expression significantly attenuated the proliferation, migration, and invasion abilities of HTR8/SVneo cells, accompanied with the obviously decreased expression levels of P53, RhoA, Bcl-2, Bax, and MMP-9, whereas the upregulated MNSFβ expression in HTR8/SVneo cells represented the inverse effects. Furthermore, expression levels of MNSFβ and RhoA in first-trimester human placental villus tissues of RM patients were significantly decreased compared to that of NP women. <b><i>Conclusion:</i></b> These data suggested that MNSFβ promotes proliferation and migration of human EVT cells, probably via the P53 signaling pathway, and the deficiency of MNSFβ in placental villi might lead to early pregnancy loss by reducing proliferation and invasion activities of EVTs.

Expression of N-Acetylglucosaminyltransferase III Promotes Trophoblast Invasion and Migration in Early Human Placenta

2018 ◽  
Vol 26 (10) ◽  
pp. 1373-1381
Author(s):  
Qinyin Deng ◽  
Xiru Liu ◽  
Zhongmei Yang ◽  
Lan Xie
Keyword(s):  
Flow Cytometric Analysis ◽  
Gelatin Zymography ◽  
Placental Tissue ◽  
First Trimester ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Trophoblast Invasion ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Decidual Cells ◽  
And Migration

Introduction: Trophoblast migration and invasion at the maternal–fetal interface are crucial events for normal placentation and successful pregnancy. This progress is well controlled by many placenta-specific factors. Inadequate trophoblast invasion results in poor placenta plantation or even complications such as preeclampsia. It has been shown that N-acetylglucosaminyltransferase III (GnT-III) participates in tumor invasion and metastasis as a suppressor; however, the expression of GnT-III and its role in normal pregnancy is unclear. Our objective was to characterize GnT-III expression and function during placental development and identify the underlying mechanisms. Methods: The expression of GnT-III in human placental tissue from the first trimester was determined by immunohistochemistry. The HTR8/SVneo cell line was used to investigate the effects of GnT-III on proliferation, apoptosis, migration/invasion, matrix metalloproteinase (MMP) 2/9 activity, and the expression of the tissue inhibitor of metalloproteinase (TIMP) 1/2 using cell 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays, flow cytometric analysis, transwell migration/invasion assays, gelatin zymography, and Western blot, respectively. Moreover, a placental villous explant model was employed to determine its functions in placentation. Results: In the first-trimester placental tissue, GnT-III was localized within the cytotrophoblast, the syncytiotrophoblast and the trophoblast columns of human placental villi, decidual cells, and some extravillous cells in the maternal decidua. GnT-III silencing significantly inhibited HTR8/SVneo cell invasion and migration as well as extravillous explant outgrowth. The application of GnT-III siRNA significantly attenuated MMP2/9 activity and increased TIMP1/2 expression. Discussion and Conclusion: GnT-III is expressed in trophoblasts during normal human pregnancy and is involved in regulating trophoblast function.

scholarly journals Spiral artery blood flow during pregnancy: a systematic review and meta-analysis.

2019 ◽  
Author(s):  
Veronique Schiffer ◽  
Laura Evers ◽  
Sander de Haas ◽  
Chahinda Ghossein ◽  
Salwan Al-Nasiry ◽  
...  
Keyword(s):  
Systematic Review ◽  
Blood Flow ◽  
Meta Analysis ◽  
Resistance Index ◽  
First Trimester ◽  
Trophoblast Invasion ◽  
Cochrane Library ◽  
Second Trimester ◽  
Spiral Artery ◽  
Third Trimester

Abstract Background: Downstream remodeling of the spiral arteries (SpA) decreases utero-placental resistance drastically, allowing sustained and increased blood flow to the placenta at all circumstances. We systematically evaluated available reports to visualize adaptation of spiral arteries throughout pregnancy by ultra-sonographic measurements and evaluated when this process is completed.Methods: A systematic review and meta-analysis of spiral artery flow (pulsatility index (PI), resistance index (RI) and peak systolic velocity (PSV)) was performed. English articles were obtained from Pubmed, EMBASE and Cochrane Library and included articles were assessed on quality and risk of bias. Weighted means of Doppler indices were calculated using a random-effects model. Results: In healthy pregnancies, PI and RI decreased from 0.75 (95% CI: 0.67-0.83) and 0.49 (95% CI: 0.46-0.53) in the first trimester to 0.52 (95% CI: 0.48-0.56, p=0.003) and 0.40 (95% CI: 0.38-0.42, p=0.080) in the second trimester and to 0.49 (95% CI: 0.44-0.53, p=0.510) and 0.36 (95% CI: 0.35-0.37, p=0.307) in the third trimester, respectively. In parallel, PSV altered from 0.24 m/s (95% CI: 0.17-0.31 m/s) to 0.28 m/s (95% CI: 0.22-0.34 m/s, p=0.377) and to 0.25 m/s (95% CI: 0.21-0.28 m/s, p=0.919) in the three trimesters. In absence of second and third trimester Doppler data in complicated gestation, only a difference in PI was observed between complicated and healthy pregnancies during the first trimester (1.49 vs 0.76, p<0.001). Although individual studies have identified differences in PI between SpA located in the central part of the placental bed versus those located at its periphery, this meta-analysis could not confirm this (p=0.349).Conclusions: This review and meta-analysis concludes that an observed decrease of SpA PI and RI from the first towards the second trimester parallels the physiological trophoblast invasion converting SpA during early gestation, a process completed in the midst of the second trimester. Higher PI and RI were found in SpA of complicated pregnancies compared to healthy pregnancies, possibly reflecting suboptimal utero-placental circulation. Longitudinal studies examining comprehensively the predictive value of spiral artery Doppler for complicated pregnancies are yet to be carried out.

INFLUENCE OF GLUCOSE AND INSULIN OF PROSTACYCLIN SYNTHESIS IN CULTURED TR0PH0BLAST CELLS

1987 ◽  
Author(s):  
I Rákóczi ◽  
Gy Geró ◽  
J Demeter ◽  
I Gáti
Keyword(s):  
New England ◽  
Early Pregnancy ◽  
Horse Serum ◽  
Physiological Role ◽  
First Trimester ◽  
Serum Glucose ◽  
Trophoblast Invasion ◽  
Trophoblast Cells ◽  
Specific Radioimmunoassay ◽  
High Concentrations

It is known that placental cells can produce prostacyclin /PGI2/. At present, the physiological role of trophoblast PGI2 production can only be speculative. PGI2 produced by trophoblast may help to prevent the platelet aggregation and thrombosis in spiral arteries and it can also explain the maintance of, and blood flow through, the spiral arteries during endovascular trophoblast invasion in early pregnancy. It has been previously shown that increased glucose concentrations in the incubation fluid can inhibit the formation of PGI2 by rat aortic rings. The aim of present investigation was to study the effect of glucose and insulin on the generation of PGI? by trophoblast obtained from early pregnancy. Trophoblast tissue was obtained immediately from surgical termination of first trimester pregnancy /9 specimens/. Trophoblast was cultured using the method of Jogee et al. Cells obtained from trypsinizaticn were cultured at a density of 2×105 cells/ml in medium 199 containing 10% horse,serum. Glucose /5.5, 16.5 and 33mmol/l / and insulin /103 , 104 and 106 mU/1 / were added to culture and the effect on 6-oxo-PGF2 production over a 24-hr incubation was assessed. Control cultures were incubated without glucose and insulin. The concentration of 6-oxo-PGF2 in culture supernatans were measured by specific radioimmunoassay /3H-6-oxo-PGF1, RIA-kit, New England Nuclear, USA /.There was a significant decrease in 6-keto-PGF10c production by trophoblast cells incubated with increased glucose concentrations /16.5 and 33 mmol/1 / compared to controls / p<0.001/. In contrast, insulin in growth medium did not have any effects on the PGI production. These data suggest that high concentrations of 2 glucose inhibit PGIp production by cultured trophoblast cells. This decreased PGIp synthesis may impair the blood supply of trophoblast which could play a role in the development of congenital anomalies in pregnant women with poorly controlled diabetes mellitus in the first trimester of pregnancy.

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.

scholarly journals BMP6 Mediates BMP2-Increased Human Trophoblast Invasion

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A747-A747
Author(s):  
Jianye Deng ◽  
Yan Li
Keyword(s):  
Molecular Mechanisms ◽  
First Trimester ◽  
Bone Morphogenetic Protein 2 ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Mrna Levels ◽  
Ongoing Research ◽  
Human Trophoblast ◽  
Protein Levels ◽  
Regulatory Effects

Abstract TGF-β superfamily proteins play divergent roles in regulating human extravillous trophoblast (EVT) invasion and their coordinated effects are essential for adequate placentation during pregnancy 1. Bone morphogenetic protein 2 (BMP2), which belongs to the BMP subfamily of TGF-β superfamily, has been shown to promote human EVT invasion and the acquisition of endothelial-like phenotype 2,3. It has been reported that BMP2 promotes EVT invasion by up-regulating Activin A, a growth factor which also belongs to TGF-β superfamily. However, whether BMP6 mediates the pro-invasive effect of BMP2 has yet to be determined. Herein, we firstly treated immortalized trophoblast cells (HTR8/SVneo) with recombinant BMP2 protein for 6 and 24 hrs, and our bulk-RNA sequencing results demonstrated significantly increased BMP6 mRNA levels after BMP2 treatment. Furthermore, we confirmed the up-regulatory effects of BMP2 on BMP6 mRNA and protein levels in both HTR8/SVneo and primary EVTs isolated from first-trimester villi. Notably, siRNA-mediated down-regulation of BMP6 significantly attenuated both basal and BMP2-induced cell invasion in HTR8/SVneo cells as measured by Matrigel-coated transwell invasion assay. In summary, our results firstly demonstrated the up-regulatory effect of BMP2 on BMP6 expression in human trophoblasts and identified the mediation role of BMP6 in BMP2-promoted EVT invasion, suggesting the interplay between BMP subfamily members during EVT invasion regulation. Our ongoing research focusing the underlying molecular mechanisms and signaling pathways could further benefit the advancement of diagnostic and therapeutic strategies for EVT invasion dysregulation-related pregnancy disorders, e.g., pre-eclampsia. Reference: (1) Li Yan et al., Trends Endocrinol Metab 2021 18: S1043-2760(20)30266-6. (2) Hong-Jin Zhao et al., FASEB J 2020;34(2):3151-3164. (3) Hong-Jin Zhao et al., Cell Death Dis 2018;9(2):174.

scholarly journals Blunted erythropoietin production and decreased erythropoiesis in early pregnancy [see comments]

Blood ◽  
1991 ◽  
Vol 78 (1) ◽  
pp. 89-93
Author(s):  
Y Beguin ◽  
G Lipscei ◽  
H Thoumsin ◽  
G Fillet
Keyword(s):  
Early Pregnancy ◽  
Cell Mass ◽  
First Trimester ◽  
Normal Pregnancy ◽  
Entire Group ◽  
Third Trimester ◽  
Serum Transferrin Receptor ◽  
Erythropoietin Production ◽  
Early Postpartum ◽  
First Trimester Of Pregnancy

After decreasing in the first trimester of pregnancy, the total red blood cell mass increases in the second and third trimesters to peak at term at about 120% to 125% of nonpregnant values, but how this is brought about by changes in the rate of erythropoiesis is not known. We evaluated erythropoiesis by measuring serum transferrin receptor (TfR) levels in 406 women during normal pregnancy (N = 317), at delivery (N = 63), or in the early postpartum (N = 27). Despite the presence of the placenta and the frequent occurrence of iron deficiency, TfR levels remained low in the first two trimesters and increased in the third trimester and at delivery. To explain why erythropoiesic activity was relatively low in early pregnancy, we also measured serum immunoreactive erythropoietin (Epo) in relation to the degree of anemia. There was a very strong correlation between serum TfR and Epo levels in the entire group (r = .59, P less than .0001) as well as in each period of pregnancy. Epo levels remained low for the degree of anemia and did not correlate with hematocrit in the first two trimesters, but recovered afterwards. In the early postpartum, Epo production and erythropoiesis were normal. We conclude that: (1) erythropoiesis is decreased in the first part of pregnancy but increases afterwards; and (2) blunted Epo production in early pregnancy could be responsible for that observation.

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