Differentiation of first trimester cytotrophoblast to extravillous trophoblast involves an epithelial–mesenchymal transition

Placenta ◽  
2015 ◽  
Vol 36 (12) ◽  
pp. 1412-1418 ◽  
Author(s):  
Sonia DaSilva-Arnold ◽  
Joanna L. James ◽  
Abdulla Al-Khan ◽  
Stacy Zamudio ◽  
Nicholas P. Illsley
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
First Trimester ◽  
Extravillous Trophoblast ◽  
Mesenchymal Transition

scholarly journals HYPOXIA AND REPRODUCTIVE HEALTH: Oxygen and development of the human placenta

Reproduction ◽  
2021 ◽  
Vol 161 (1) ◽  
pp. F53-F65 ◽  
Author(s):  
Graham J Burton ◽  
Tereza Cindrova-Davies ◽  
Hong wa Yung ◽  
Eric Jauniaux
Keyword(s):  
Oxidative Stress ◽  
Human Placenta ◽  
Epithelial Mesenchymal Transition ◽  
First Trimester ◽  
Extravillous Trophoblast ◽  
Low Oxygen ◽  
Placental Development ◽  
Mesenchymal Transition ◽  
Oxygen Concentrations

Development of the human placenta takes place in contrasting oxygen concentrations at different stages of gestation, from ~20 mmHg during the first trimester rising to ~60 mmHg at the start of the second trimester before gradually declining to ~40 mmHg at term. In view of these changes, the early placenta has been described as ‘hypoxic’. However, placental metabolism is heavily glycolytic, supported by the rich supply of glucose from the endometrial glands, and there is no evidence of energy compromise. On the contrary, the trophoblast is highly proliferative, with the physiological low-oxygen environment promoting maintenance of stemness in progenitor populations. These conditions favour the formation of the cytotrophoblastic shell that encapsulates the conceptus and interfaces with the endometrium. Extravillous trophoblast cells on the outer surface of the shell undergo an epithelial-mesenchymal transition and acquire invasive potential. Experimental evidence suggests that these changes may be mediated by the higher oxygen concentration present within the placental bed. Interpreting in vitro data is often difficult, however, due to the use of non-physiological oxygen concentrations and trophoblast-like cell lines or explant models. Trophoblast is more vulnerable to hyperoxia or fluctuating levels of oxygen than to hypoxia, and some degree of placental oxidative stress likely occurs in all pregnancies towards term. In complications of pregnancy, such as early-onset pre-eclampsia, malperfusion generates high levels of oxidative stress, causing release of factors that precipitate the maternal syndrome. Further experiments are required using genuine trophoblast progenitor cells and physiological concentrations to fully elucidate the pathways by which oxygen regulates placental development.

scholarly journals The Early Pregnancy Human Placenta Shares Hypomethylation Patterns Characteristic of Solid Tumors

2017 ◽  
Author(s):  
Akpéli V. Nordor ◽  
Djamel Nehar-Belaid ◽  
Sophie Richon ◽  
David Klatzmann ◽  
Dominique Bellet ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Drug Targets ◽  
Large Scale ◽  
Epithelial Mesenchymal Transition ◽  
Time Window ◽  
Expression Profiles ◽  
Colon Adenocarcinoma ◽  
First Trimester ◽  
Maternal Blood ◽  
Mesenchymal Transition

ABSTRACTBackgroundThe placenta relies on phenotypes that are characteristic of cancer to successfully implant the embryo in the uterus during early pregnancy. Notably, it has to invade its host tissues, promote angiogenesis, while surviving hypoxia, and escape the immune system. Similarities in DNA methylation patterns between the placenta and cancers suggest that common epigenetic mechanisms may be involved in regulating these behaviors.ResultsWe show here that megabase-scale patterns of hypomethylation distinguish first from third trimester chorionic villi in the placenta, and that these patterns mirror those that distinguish many tumors from corresponding normal tissues. We confirmed these findings in villous cytotrophoblasts isolated from the placenta and identified a time window at the end of the first trimester, when these cells come into contact with maternal blood as the likely time period for the methylome alterations. Furthermore, the large genomic regions affected by these patterns of hypomethylation encompass genes involved in pathways related to epithelial-mesenchymal transition (EMT), immune response and inflammation. Analyses of expression profiles corresponding to genes in these hypomethylated regions in colon adenocarcinoma tumors point to networks of differentially expressed genes previously implicated in carcinogenesis and placentogenesis, where nuclear factor kappa B (NF-kB) is a key hub.ConclusionTaken together, our results suggest the existence of epigenetic switches involving large-scale changes of methylation in the placenta during pregnancy and in tumors during neoplastic transformation. The characterization of such epigenetic switches might lead to the identification of biomarkers and drug targets in oncology as well as in obstetrics and gynecology.

scholarly journals Epithelial-mesenchymal transition during extravillous trophoblast differentiation

2016 ◽  
Vol 10 (3) ◽  
pp. 310-321 ◽  
Author(s):  
Jessica E. Davies ◽  
Jürgen Pollheimer ◽  
Hannah E. J. Yong ◽  
Maria I. Kokkinos ◽  
Bill Kalionis ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Extravillous Trophoblast ◽  
Trophoblast Differentiation ◽  
Mesenchymal Transition

scholarly journals Upregulation of circRNA hsa_circ_0008726 in Pre-eclampsia Inhibits Trophoblast Migration, Invasion, and EMT by Regulating miR-345-3p/RYBP Axis

2021 ◽  
Author(s):  
Chang Shu ◽  
Peng Xu ◽  
Jun Han ◽  
Shumei Han ◽  
Jin He
Keyword(s):  
Cell Migration ◽  
Epithelial Mesenchymal Transition ◽  
Extravillous Trophoblast ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Rnase R ◽  
Mesenchymal Transition ◽  
Potential Biomarker ◽  
Rna Immunoprecipitation

AbstractAccumulating evidence shows that impaired spiral artery remodeling, placental dysfunction, and insufficient trophoblast infiltration contribute to the etiology and pathogenesis of pre-eclampsia (PE). circRNAs are a class of endogenous non-coding RNAs implicated in the pathogenesis of many diseases, including PE. This study aims to investigate the role of circRNA hsa_circ_0008726 in regulating the migration and invasion of extravillous trophoblast cells. RNase R assay was performed to confirm that circ_0008726 was a circular transcript. The expression of circ_0008726, RYBP, and miR-345-3p was examined by qRT-PCR. The functional interaction between miR-345-3p and circ_0008726 or RYBP was confirmed using dual-luciferase reporter assay and RNA immunoprecipitation (RIP). Cell migration and invasion ability was analyzed by Transwell assays. Western blot was used for the quantification of RYBP protein level. Circ_0008726 expression was significantly increased in PE placenta tissues as compared with normal placenta tissues. Circ_0008726 was resistant to RNase R digestion and was predominately located in the cytoplasm of HTR-8/SVneo cells. Silencing circ_0008726 promoted cell migration and EMT (epithelial-mesenchymal transition), while circ_0008726 overexpression suppressed these processes. Mechanistically, circ_0008726 sponged miR-345-3p to negatively regulate its expression, and miR-345-3p negatively modulated the expression of RYBP. In PE samples, the expression level of circ_0008726 was negatively correlated with miR-345-3p level, but was positively correlated with RYBP expression. Transfection of miR-345-3p mimic or RYBP knockdown counteracted the effects of circ_0008726 overexpression on cell migration and EMT. Our data demonstrate the upregulation of circ_0008726 in PE placenta, which inhibits the migration, invasion, and EMT of HTR-8/SVneo cells by targeting miR-345-3p/RYBP axis. These data suggest that circ_0008726 could be a potential biomarker and therapeutic target for PE.

scholarly journals Expression levels of Tyro3 Receptor Kinase in the Decidua of the First Trimester Unexplained Recurrent Pregnancy Loss

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Necdet Demir
Keyword(s):  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Epithelial Mesenchymal Transition ◽  
Thrombus Formation ◽  
First Trimester ◽  
Receptor Kinase ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Healthy Pregnancy ◽  
Tam Receptors

Spontaneous loss is seen 12-15 % in all pregnancies. More than %50 of those patients do not have a defined etiology, so they are named unexplained Recurrent Pregnancy Loss (URPL). Studies in recent years have made us think that Pregnancy Losses may be related to insufficient decidualization and undetected prothrombotic problems. Tyro3 receptor kinase (RTK) is a member of TAM receptors and has been reported to have an important role in migration, Epithelial-mesenchymal transition (EMT), and platelet aggregation. There is not sufficient knowledge about expression levels of Tyro3 RTK in human first-trimester URPL decidua (URPLD). By immunohistochemistry, immunoblotting, and qPCR, we investigated the expression of Tyro3 RTK in the decidua of human first-trimester termination healthy pregnancy (TPD)(n:6) and URPLD(n:6), and human endometrium (CE)(n:6). Our results suggest that Tyro3 RTK expression significantly decreases with pregnancy and then returns to levels of CE for URPLD. Considering the role of Tyro3 RTK in platelet activation and thrombus formation, it suggests that this decrease observed in TPD may prevent the formation of prothrombosis which can prevent placental flow, and thus, hemostasis could be regulated in pregnancy through Tyro3 RTK. Although Tyro3 RTK decrease in TPD, locally increase on TPD, and also decrease on URPLD of Tyro3 RTK on DSCs makes us think, which Tyro3 RTK has a regulating role for EMT formation on DSCs and may participate in implantation and survival processing of the embryo through DSCs. If those predictions are supported by further functional analyses, one of the causes of URPLD can be enlightened.

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