Trophoblast deportation part II: A review of the maternal consequences of trophoblast deportation

Pantham, Priyadarshini; Askelund, Kathryn; Chamley, Larry

doi:10.1016/j.placenta.2011.06.019

Cited by 37 publications

(27 citation statements)

References 71 publications

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“…One possibility is that the syncytiotrophoblast acts as a non-professional phagocyte, similar to what has been seen for endothelial cells [33] and mammary epithelial cells [34], and engulfs the products of cytotrophoblast apoptosis by phagocytosis [35]. It is also unclear how the apoptotic bodies in the syncytiotrophoblast cytoplasm are eliminated, but possible mechanisms include autophagy [36,37] and release by an unknown mechanism into the maternal circulation [38,39]. Indeed, circulating trophoblast fragments have been assigned a role in the pathology of preeclampsia [39,40].…”

Section: Discussionmentioning

confidence: 99%

Villous trophoblast apoptosis is elevated and restricted to cytotrophoblasts in pregnancies complicated by preeclampsia, IUGR, or preeclampsia with IUGR

et al. 2012

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Human placental villi are surfaced by an outer multinucleated syncytiotrophoblast and underlying mononucleated cytotrophoblasts. Conflicting data have attributed one, or the other, of these villous trophoblast phenotypes to undergo enhanced apoptosis in complicated pregnancies, compared to term, normotensive pregnancies. We use high-resolution confocal microscopy after co-staining for E-cadherin, as a trophoblast plasma membrane marker, and for the cleavage products of cytokeratin 18 and PARP1, as markers for caspase-mediated apoptosis, to distinguish between apoptotic cytotrophoblasts and apoptosis within the syncytiotrophoblast. We test the hypothesis that increased caspase-mediated apoptosis occurs in villi of placentas derived from pregnancies complicated by preeclampsia, intrauterine growth restriction (IUGR), or both. We find significantly elevated apoptosis in villous cytotrophoblasts from women with preeclampsia and/or IUGR, compared to term, normotensive pregnancies. Apoptosis of cytotrophoblasts in villi from complicated pregnancies appears to progress similarly to what we found previously for apoptotic cytotrophoblasts in villi from in term, normotensive pregnancies. Notably, caspase-mediated apoptosis was not detectable in regions with intact syncytiotrophoblast, suggesting strong repression of apoptosis in this trophoblast phenotype in vivo. We suggest that the elevated apoptosis in cytotrophoblasts in preeclampsia contributes to the placental dysfunction characteristic of this disorder. We also propose that repression of apoptosis in the syncytiotrophoblast is important to prevent apoptosis sweeping throughout the syncytium, which would result in widespread death of this essential interface for maternal-fetal exchange.

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Section: Discussionmentioning

confidence: 99%

Villous trophoblast apoptosis is elevated and restricted to cytotrophoblasts in pregnancies complicated by preeclampsia, IUGR, or preeclampsia with IUGR

et al. 2012

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“…Thus, aberrant maternal immune responses, such as those observed in preeclampsia, may result from the quantitative and/or qualitative changes in the deported trophoblast debris [35]. What would be the impact on the maternal immune system by too large or too small amounts of syncytial debris?…”

Section: Trophoblast Proliferation Apoptosis and Turnover In Preeclmentioning

confidence: 99%

Morphological changes of placental syncytium and their implications for the pathogenesis of preeclampsia

Roland

Ren

et al. 2015

Cell. Mol. Life Sci.

110

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Preeclampsia is a hypertensive disease that complicates many pregnancies, typically presenting with new-onset or worsening hypertension and proteinuria. It is well recognized that the placental syncytium plays a key role in the pathogenesis of preeclampsia. This review summarizes the findings pertaining to the structural alterations in the syncytium of preeclamptic placentas and analyzes their pathological implications for the development of preeclampsia. Changes in the trophoblastic lineage, including those in the proliferation of cytotrophoblasts, the formation of syncytiotrophoblast through cell fusion, cell apoptosis and syncytial deportation, are discussed in the context of preeclampsia. Extensive correlations are made between functional deficiencies and the alterations on the levels of gross anatomy, tissue histology, cellular events, ultrastructure, molecular pathways, and gene expression. Attention is given to the significance of dynamic changes in the syncytial turnover in preeclamptic placentas. Specifically, experimental evidences for the complex and obligatory role of syncytin-1 in cell fusion, cell-cycle regulation at the G1/S transition, and apoptosis through AIF-mediated pathway, are discussed in detail in the context of syncytium homeostasis. Finally, the recent observations on the aberrant fibrin deposition in the trophoblastic layer and the trophoblast immature phenotype in preeclamptic placentas and their potential pathogenic impact are also reviewed.

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“…endothelial cells, cells of immune system, platelets) which release exosomes and attribute to increase in overall exosome number. This noticeable finding is consistent to previously conducted studies [125][126][127][128].…”

Section: Placental-derived Exosomes In Maternal Circulationsupporting

confidence: 93%

First trimester plasma-derived exosomal proteins: putative biomarker for early detection of pathological pregnancies

Sarker¹

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Background: Of the 130 million babies born each year, 8 million die before their first birthday. A contributing factor in many of these deaths is poor pregnancy outcome as a result of complications of pregnancy. Preeclampsia (PE) and Gestational Diabetes Mellitus (GDM) are the common pregnancy complications that have no effective antenatal treatment other than steroid administration and timely delivery. Each occurs with an incidence of 5-10% and is responsible for the majority of obstetric and paediatric morbidity and mortality. These can permanently impact on lifelong health.Early detection of disease risk and onset is the first step in implementing efficacious treatment and improving patient outcome. In the context of antenatal screening, the objective is to identify biomarkers (e.g. proteins) that are informative of the risk of asymptomatic pregnant women subsequently developing complications of pregnancy. Recent studies highlight the putative utility of tissue-specific nanovesicles (i.e. exosomes) in the diagnosis of disease onset and treatment monitoring. It was hypothesized that presymptomatic women who subsequently develop pregnancy complications display altered exosome profile (i.e. concentration and/or protein content) at first trimester of pregnancy (i.e. 6-12 weeks). The general aim of this thesis was to identify blood-borne biomarkers (i.e. exosomes) that may be used at the first antenatal visit to identify presymptomatic women who are at risk of developing complications of pregnancy. Methods:A time-series experimental design was used to establish pregnancy-associated changes in maternal plasma exosome concentrations during first trimester. Serial samples of plasma were collected from normal healthy pregnant women (n=10) at 6, 7, 8, 9, 10, 11 and 12 weeks of gestation. Plasma samples from pregnant women at 11-14 weeks of gestation who developed preeclampsia (n=15) and gestational diabetes mellitus (n=7) were also collected. Exosomes were isolated by differential and buoyant density centrifugation and characterised by size distribution and morphology using nanoparticles tracking analysis (NTA; NanoSight™) and transmission electron microscopy (TEM) respectively. The total number of exosome vesicles and placenta-derived exosome vesicles were determined by quantifying immunoreactive exosomal CD63 and a placentaspecific marker (PLAP) by ELISA. Finally, the differentially expressed exosomal proteins and peptides were identified by Liquid Chromatography and Mass Spectrometry based approaches (LC-MS/MS). Statistical analysis was performed using the Graph Pad Prism software.ii Results: EM and NTA identified the presence of 50 -120 nm spherical vesicles in maternal plasma as early as 6 weeks of pregnancy. The number of exosomes in maternal circulation increased significantly (ANOVA, p=0.002) with the progression of pregnancy (from 6 to 12 weeks). The concentration of placenta-derived exosomes in maternal plasma (i.e. PLAP + ) increased progressively with gestational age, from 6 weeks 70.6 ± 5.7 pg/ml t...

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Trophoblast deportation part II: A review of the maternal consequences of trophoblast deportation

Cited by 37 publications

References 71 publications

Villous trophoblast apoptosis is elevated and restricted to cytotrophoblasts in pregnancies complicated by preeclampsia, IUGR, or preeclampsia with IUGR

Villous trophoblast apoptosis is elevated and restricted to cytotrophoblasts in pregnancies complicated by preeclampsia, IUGR, or preeclampsia with IUGR

Morphological changes of placental syncytium and their implications for the pathogenesis of preeclampsia

First trimester plasma-derived exosomal proteins: putative biomarker for early detection of pathological pregnancies

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