Trophoblast debris extruded from preeclamptic placentae activates endothelial cells: A mechanism by which the placenta communicates with the maternal endothelium

Shen, Fang; Wei, Jia; Snowise, Saul; DeSousa, Joana; Stone, Peter; Viall, Chez A.; Chen, Q.; Chamley, Larry

doi:10.1016/j.placenta.2014.07.009

Cited by 56 publications

(39 citation statements)

References 27 publications

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“…In more physiological studies, we showed that macrovesicles from preeclamptic placentae can also cause endothelial cell activation whereas vesicles from control normotensive placentae do not (Shen et al 2014). These effects were dependent on the macrovesicles being phagocytosed by the endothelial cells and were associated with changes in nitric oxide and calcium signaling in the endothelial cells (Chen et al 2013).…”

Section: Endothelial Cellsmentioning

confidence: 94%

Placental Extracellular Vesicles and Feto-Maternal Communication

Tong

Chamley

2015

Cold Spring Harbor Perspectives in Medicine

122

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The human placenta is an anatomically unique structure that extrudes a variety of extracellular vesicles into the maternal blood (including syncytial nuclear aggregates, microvesicles, and nanovesicles). Large quantities of extracellular vesicles are produced by the placenta in both healthy and diseased pregnancies. Since their first description more than 120 years ago, placental extracellular vesicles are only now being recognized as important carriers for proteins, lipids, and nucleic acids, which may play a crucial role in feto-maternal communication. Here, we summarize the current literature on the cargos of placental extracellular vesicles and the known effects of such vesicles on maternal cells/systems, especially those of the maternal immune and vascular systems.T he placenta is an unusual organ with a short and defined life span. The human placenta is a fetal organ that sits between the fetus and its mother, connecting the fetus to the maternal blood supply. It is highly invasive and the entire surface of the placenta is in contact with the maternal circulation during most of gestation. Therefore, the human placenta effectively behaves as one wall of a maternal "blood vessel." This phenomenon is quite remarkable because, being a fetal organ, the placenta is in essence a semiallogeneic tissue graft in normal pregnancy and a complete allograft in surrogate or donor egg pregnancies. Therefore, the placenta is nature's only tissue graft.The human placenta has a villous (branching) structure. The surface of placental villi is covered by the multinucleated syncytiotrophoblast that is terminally differentiated and is not mitotically active. The growth and replenishment of the syncytiotrophoblast is effected by fusion of underlying mononuclear cytotrophoblasts into this layer. Beneath the cytotrophoblasts is the mesenchymal core of the villus with fetal blood vessels. The syncytiotrophoblast is a remarkable cell, which at least in theory, is a single cell covering the entire surface of the placenta and is the immunological barrier between the maternal immune system and the fetus. In a normal term placenta, the syncytiotrophoblast has an area of some 11 -13 m 2 (Mayhew 2014). However, the syncytiotrophoblast can be denuded, leaving areas lined by fibrinoid rather than syncytiotrophoblast and presumably before the laying down of this fibrinoid, cells of the villous mesenchymal core or cytotrophoblasts are exposed to the maternal blood, at least temporarily.

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Section: Endothelial Cellsmentioning

confidence: 94%

Placental Extracellular Vesicles and Feto-Maternal Communication

Tong

Chamley

2015

Cold Spring Harbor Perspectives in Medicine

122

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“…Since SNAs are as yet difficult to harvest from maternal blood, we have used readily accessible SNAs obtained from a placental explant model [29,[40][41][42] to assessed the quantity and quality of the DNA content of SNAs and the utility of this material for genetic diagnostics. The…”

Section: Discussionmentioning

confidence: 99%

Detection of Fetal Sex, Aneuploidy and a Microdeletion from Single Placental Syncytial Nuclear Aggregates

Holland

Kroneis²,

El‐Heliebi³

et al. 2016

Fetal Diagn Ther

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Objectives: A key problem in prenatal screening using extra-embryonic cells is the feasibility of extracting usable DNA from a small number of cells. Syncytial nuclear aggregates (SNAs) are multinucleated structures shed from the placenta. This study assesses the potential of SNAs as a source of fetal DNA for the detection of genetic abnormalities. Methods: SNAs were collected in vitro. Whole-genome amplification was used to amplify DNA from single SNAs, and DNA quality and quantity was assessed by spectrophotometry and PCR. Confocal microscopy was used to count nuclei within SNAs, determine metabolic activity and investigate DNA damage. Fetal sex and chromosomal/genetic abnormalities were investigated with array-comparative genomic hybridization (aCGH). Results: DNA was amplified from 81% of the individual SNAs. A mean of 61 ± 43 nuclei were found per SNA. DNA strand breaks were found in 76% of the SNAs. Seventy-five percent of SNAs yielded whole-genome-amplified DNA of sufficient quality for aCGH after storage and shipping. Individual SNAs from the same pregnancy reliably gave the same chromosomal profile, and fetal sex and trisomies could be detected. A microdeletion was detected in one pregnancy. Conclusion: SNAs could provide a source of extra-embryonic DNA for the prenatal screening/diagnosis of fetal sex and chromosomal and sub-chromosomal genetic abnormalities.

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“…14,33 A recent study of ours has shown that trophoblastic debris from preeclamptic placentae contains the inflammatory cytokine IL-1β, which may be partly responsible for inducing endothelial cell activation. 9 IL-1β is an important mediator of the inflammatory response and it is possible that it also has an important role in maternal endothelial dysfunction in preeclampsia. 34 In the current study, our data show that when endothelial cells were exposed to inflammatory cytokine, IL-1β, an increase in ICAM-1 expression was seen.…”

Section: Discussionmentioning

confidence: 99%

“…7,8 We have recently shown that the trophoblastic debris produced from preeclamptic placentae or placentae that have been treated with preeclamptic sera is 'dangerous/toxic'. 9 When phagocytosed, this dangerous/ toxic trophoblastic debris leads to endothelial cell activation and secretion of inflammatory cytokines, 9,10 a process seen in preeclampsia. Other studies also reported the increased levels of inflammatory cytokines in women with preeclampsia.…”

Section: Introductionmentioning

confidence: 99%

The anti-inflammatory effect of calcium for preventing endothelial cell activation in preeclampsia

et al. 2015

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Preeclampsia is a disorder of pregnancy characterized by endothelial activation. It is believed to be a response to a 'toxin(s)' from the placenta including trophoblastic debris and inflammatory cytokines. Calcium is known to reduce the risk of preeclampsia but the mechanism of its protective effect remains unknown. In this study, we investigated the potential mechanism(s) of calcium supplementation for preventing endothelial activation induced by trophoblastic debris. Trophoblastic debris was harvested from preeclamptic placentae and also from first-trimester placentae, which had been treated with preeclamptic sera. Endothelial cells were then cultured with trophoblastic debris in the presence of calcium. Endothelial activation was measured by quantifying endothelial cell-surface intercellular adhesion molecule-1 (ICAM-1) and by U937 monocyte adhesion to endothelial cells. The expression of ICAM-1 and U937 adhesion to endothelial cells were significantly reduced following exposure of endothelial cells to trophoblastic debris from preeclamptic placenta or from first-trimester placentae treated with preeclamptic sera in the presence of calcium compared with treatment without calcium. The expression of ICAM-1 was also significantly reduced following exposure of endothelial cells to trophoblastic debris with the nitric oxide donor or following treatment of endothelial cells with interleukin (IL)-1β in the presence of calcium. Our study demonstrated that calcium supplementation prevented endothelial cell activation induced by trophoblastic debris from preeclamptic placentae. The nitric oxide synthase (NOS) pathway and anti-inflammatory effects are involved in the action of calcium on endothelial cell activation. These findings may suggest, at least in part, the protective mechanism of calcium supplementation on preeclampsia.

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Trophoblast debris extruded from preeclamptic placentae activates endothelial cells: A mechanism by which the placenta communicates with the maternal endothelium

Cited by 56 publications

References 27 publications

Placental Extracellular Vesicles and Feto-Maternal Communication

Placental Extracellular Vesicles and Feto-Maternal Communication

Detection of Fetal Sex, Aneuploidy and a Microdeletion from Single Placental Syncytial Nuclear Aggregates

The anti-inflammatory effect of calcium for preventing endothelial cell activation in preeclampsia

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