E-cadherin in the assessment of aberrant placental cytotrophoblast turnover in pregnancies complicated by pre-eclampsia

Brown, Lauren; Lacey, H; Baker, Philip N.; Crocker, Ian

doi:10.1007/s00418-005-0051-7

Cited by 82 publications

(55 citation statements)

References 32 publications

(30 reference statements)

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“…Dual labeling of Mtd with cyclin E1 revealed that Mtd was present during the G 1 phase of the cell cycle in the early first trimester CTs of floating and anchoring villi (Figure 2a, data not shown), with coexpression decreasing in the late first trimester (data not shown). To confirm that Mtd expression was localized to CTs during the early first trimester, we performed coexpression studies of Mtd with the cytotrophoblast marker, E-cadherin 33 ( Figure 2b). It is noted that Mtd expression was not restricted to cyclin E1-positive cells, as cells that were presumably undergoing mitosis, as shown by chromosomal patterning (Figure 2c) and Ki67 (Figure 2c, bottom panel), also displayed Mtd expression in the nucleus.…”

Section: Resultsmentioning

confidence: 99%

Mtd/Bok takes a swing: proapoptotic Mtd/Bok regulates trophoblast cell proliferation during human placental development and in preeclampsia

et al. 2009

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We have previously reported that matador/Bcl-2 ovarian killer (Mtd/Bok), a proapoptotic member of the Bcl-2 family, regulates human trophoblast apoptosis and that its levels are elevated in severe preeclamptic pregnancy. Herein, we show that Mtd is also involved in the regulation of proliferation in normal and pathological placentae. Mtd was found in proliferating trophoblast cells during early placental development and in preeclampsia (PE). The main isoform of Mtd associated with trophoblast proliferation was Mtd-L, the full-length isoform, which preferentially localized to the nuclear compartment in proliferating cells, whereas during apoptosis it switched localization to the cytoplasm where it associated with mitochondria. Mtd expression in proliferating cells colocalized with cyclin E1, a G 1 /S phase cell cycle regulator. MtdL-specific knockdown in the early first trimester villous explants and in HEK293 revealed a direct effect of Mtd-L on cyclin E1 expression and cell cycle progression. We conclude that Mtd-L functions to regulate trophoblast cell proliferation during early placentation and that the elevated levels of Mtd found in PE may contribute to increased trophoblast proliferation accompanying this devastating disorder of pregnancy.

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Section: Resultsmentioning

confidence: 99%

Mtd/Bok takes a swing: proapoptotic Mtd/Bok regulates trophoblast cell proliferation during human placental development and in preeclampsia

et al. 2009

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“…14 Furthermore, immunohistochemical and morphometric analyses of preeclamptic placentae revealed an increase in proliferative activity of cytotrophoblast. 31,32 Therefore, these diseases might represent divergent end points resulting from Understanding the mechanisms that govern CT cell survival in the human placenta, and the selective expression of GCM1 in CT destined for syncytial fusion or in EV-CT remodeling spiral arteries will improve our perception of the early origins of severe IUGR and preeclampsia caused by the so-called 'placental insufficiency.' Further studies of GCM1 regulation, together with an integration of stereologically determined villous trophoblast structure, are needed.…”

Section: Discussionmentioning

confidence: 99%

Glial cell missing-1 transcription factor is required for the differentiation of the human trophoblast

et al. 2009

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Mammalian placentation is a highly regulated process and is dependent on the proper development of specific trophoblast cell lineages. The two major types of trophoblast, villous and extravillous, show mitotic arrest during differentiation. In mice, the transcription factor, glial cell missing-1 (Gcm1), blocks mitosis and is required for syncytiotrophoblast formation and morphogenesis of the labyrinth, the murine equivalent of the villous placenta. The human homolog GCM1 has an analogous expression pattern, but its function is presently unknown. We studied GCM1 function in the human-derived BeWo choriocarcinoma cell line and in first trimester human placental villous and extravillous explants. The GCM1 expression was either inhibited by siRNA and antisense oligonucleotides methods or upregulated by forskolin treatment. Inhibition of GCM1 resulted in an increased rate of proliferation, but prevented de novo syncytiotrophoblast formation in syncytially denuded floating villous explants. GCM1 inhibition prevented extravillous differentiation along the invasive pathway in extravillous explants on matrigel. By contrast, forskolin-induced expression of GCM1 reduced the rate of proliferation and increased the rate of syncytialization in the floating villous explant model. Our studies show that GCM1 has a distinct role in the maintenance, development and turnover of the human trophoblast. Alterations in GCM1 expression or regulation may explain several aspects of two divergent severe placental insufficiency syndromes, namely preeclampsia and intrauterine growth restriction, which cause extreme preterm birth. Successful mammalian pregnancy demands two key steps in placental development, both of which are regulated by differentiation of the epithelial trophoblast lineage. 1 First, maternal blood flow to the implantation site must increase exponentially to serve the demands of the rapidly growing fetus. This is achieved through the invasion of extravillous cytotrophoblasts (EV-CTs) from the base of the placenta into the maternal uterine stroma, where they surround and dilate the distal portions of the utero-placental arteries. 2 Second, the increased delivery of maternal blood to the placenta must be matched by an exchanger organ to transfer nutrients, remove waste products and respiratory gases between the mother and the developing fetus. This requirement is achieved through the expansion and differentiation of the chorionic villous trees of the placenta. These villi are covered by a villous trophoblast compartment comprising of villous cytotrophoblasts (V-CTs) beneath a continuous multinucleated layer of syncytiotrophoblast (SCT), which is in direct contact with maternal blood. 3 In the human placenta, EV-CTs of the proximal portion of the anchoring villus cell column are proliferative, but more distal cells differentiate, as they invade and disperse into the uterine stroma. Here these cells surround and replace the smooth muscle cells of maternal uterine arteries, converting them into high-flow dilated sinusoids. The ar...

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“…90 Increased E-cadherin expression in PE may reflect excessive trophoblast proliferation, or impaired trophoblast differentiation, either of which could have adverse consequences. 91 E-cadherin protein levels are also significantly higher in PE placentae compared with normotensive placentae. 51 Thus, it was also suggested that cadherin modulation is defective in PE, as it was shown that VE-cadherin was not adequately upregulated in trophoblasts for interaction with maternal vessels.…”

Section: Altered Expression Of Emt Inducers Transcription Factors Anmentioning

confidence: 91%

Epithelial-mesenchymal transition during extravillous trophoblast differentiation

Davies

Pollheimer

Yong

et al. 2016

Cell Adhesion & Migration

209

146

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A successful pregnancy depends on the intricate and timely interactions of maternal and fetal cells. Placental extravillous cytotrophoblast invasion involves a cellular transition from an epithelial to mesenchymal phenotype. Villous cytotrophoblasts undergo a partial epithelial to mesenchymal transition (EMT) when differentiating into extravillous cytotrophoblasts and gain the capacity to migrate and invade. This review summarizes our current knowledge regarding known regulators of EMT in the human placenta, including the inducers of EMT, upstream transcription factors that control EMT and the downstream effectors, cell adhesion molecules and their differential expression and functions in pregnancy pathologies, preeclampsia (PE) and fetal growth restriction (FGR). The review also describes the research strategies that were used for the identification of the functional role of EMT targets in vitro. A better understanding of molecular pathways driven by placental EMT and further elucidation of signaling pathways underlying the developmental programs may offer novel strategies of targeted therapy for improving feto-placental growth in placental pathologies including PE and FGR.

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E-cadherin in the assessment of aberrant placental cytotrophoblast turnover in pregnancies complicated by pre-eclampsia

Cited by 82 publications

References 32 publications

Mtd/Bok takes a swing: proapoptotic Mtd/Bok regulates trophoblast cell proliferation during human placental development and in preeclampsia

Mtd/Bok takes a swing: proapoptotic Mtd/Bok regulates trophoblast cell proliferation during human placental development and in preeclampsia

Glial cell missing-1 transcription factor is required for the differentiation of the human trophoblast

Epithelial-mesenchymal transition during extravillous trophoblast differentiation

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