Maternal serum of women with pre-eclampsia reduces trophoblast cell viability: evidence for an increased sensitivity to Fas-mediated apoptosis

Neale, Donna M; Demasio, Kafui; Illuzi, J.L.; Chaiworapongsa, Tinnakorn; Romero, Roberto; Mor, Gil

doi:10.1080/jmf.13.1.39.44

Cited by 51 publications

(28 citation statements)

References 53 publications

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“…In the present study, we observed colocalization of TUNEL staining with either PECAM1-or pancytokeratin-labeled cells in AS 4.5 -treated murine dams, consistent with endothelial/trophoblast-induced apoptosis in the maternal decidua and adjacent spongiotrophoblast tissue. Several studies have investigated the role of circulating maternal factors as possible mediators of increased levels of apoptosis in villous tissues, including vascular endothelial growth factor (VEGF), tumor necrosis factor a (TNFa) [30], and interferon-c [31,32], in addition to interleukins 1, 6, and 10 [33,34]. Evidence from the current study supports the hypothesis that angiostatin, a proteolytic cleavage product of plasminogen, induces a form of FGR in mice, which is characterized by significant skeletal growth delay and edema.…”

Section: Discussionmentioning

confidence: 99%

Thrombophilic-Type Placental Pathologies and Skeletal Growth Delay Following Maternal Administration of Angiostatin4.5 in Mice

Atkinson

Mukhopadhyay

Jiang

et al. 2011

Biology of Reproduction

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During placentation, the concentration of fibrinous deposits on the surfaces of maternal vasculature plays a role in villous development and has been strongly implicated in the pathophysiology of human fetal growth restriction (FGR). Fibrinous deposits are conspicuous sites of platelet aggregation where there is local activation of the hemostatic cascade. During activation of the hemostatic cascade, a number of pro- and antiangiogenic agents may be generated at the cell surface, and an imbalance in these factors may contribute to the placental pathology characteristic of FGR. We tested the hypothesis that angiostatin(4.5) (AS(4.5)), a cleavage fragment of plasminogen liberated at the cell surface, is capable of causing FGR in mice. Increased maternal levels of AS(4.5) in vivo result in reproducible placental pathology, including an altered vascular compartment (both in decidual and labyrinthine layers) and increased apoptosis throughout the placenta. In addition, there is significant skeletal growth delay and conspicuous edema in fetuses from mothers that received AS(4.5). Maternally generated AS(4.5), therefore, can access maternal placental vasculature and have a severe effect on placental architecture and inhibit fetal development in vivo. These findings strongly support the hypothesis that maternal AS(4.5) levels can influence placental development, possibly by directly influencing trophoblast turnover in the placenta, and contribute to fetal growth delay in mice.

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Section: Discussionmentioning

confidence: 99%

Thrombophilic-Type Placental Pathologies and Skeletal Growth Delay Following Maternal Administration of Angiostatin4.5 in Mice

Atkinson

Mukhopadhyay

Jiang

et al. 2011

Biology of Reproduction

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“…The exact causes of enhanced apoptosis in preeclampsia are currently unknown. Likewise, increased apoptosis of syncytiotrophoblasts may increase the amount of syncytiotrophoblast debris, syncytial knots, that leak into the maternal circulation and generate an exaggerated systemic endothelial activation [23]. Sargent et al [24] have proposed that when syncytial knots break off in increasing amounts from the placenta and are shed into the maternal circulation they may be the cause of the systemic endothelial activation that is seen in preeclampsia ( fig.…”

Section: Apoptosis and Syncytial Knotsmentioning

confidence: 97%

Immunology of Preeclampsia

Matthiesen¹,

Berg²,

Ernerudh³

et al. 2005

Chemical Immunology and Allergy

159

119

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Preeclampsia is a placenta-dependent disorder with both local and systemic anomalies with neonatal and maternal morbidity. It is manifested late in pregnancy, but the onset is during early stages of gestation. The current hypothesis regarding the aetiology of preeclampsia is focused on maladaptation of immune responses and defective trophoblast invasion. Thus, an excessive maternal inflammatory response, perhaps directed against foreign fetal antigens, results in a chain of events including shallow trophoblast invasion, defective spiral artery remodelling, placental infarction and release of pro-inflammatory cytokines and placental fragments in the systemic circulation. During normal pregnancy, trophoblasts interact in the decidua with the unique uterine NK cells, modifying their cytokine repertoire, regulating adhesion molecules and matrix metalloproteinases. The inability of trophoblasts to accomplish these changes might be a critical factor for the onset of preeclampsia. Several cytokines, produced at the maternal-fetal interface, have an impact on trophoblast invasion. It is suggested that deficiency of interleukin-10 may contribute to enhanced inflammatory responses towards the trophoblasts elicited by e.g. tumour necrosis factor-alpha and interferon-gamma. Consequently, trophoblasts subjected to a high rate of apoptosis are hampered in their invasive capacity resulting in defective transformation of spiral arteries, hypoxia, thrombosis and infarction of the placenta. The ensuing infarction of placenta leads to leakage of increasing amounts of placental fragments and cytokines in the maternal circulation and an exaggerated systemic endothelial activation as identified in preeclampsia. So far, treatment of preeclampsia is focused on signs like hypertension, whereas attempts of modifying immune responses may be a possibility in the future.

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“…Mechanisms of disease implicated in this syndrome [1][2][3][4] include uteroplacental ischemia [5][6][7][8][9][10][11], increased trophoblast deportation [12][13][14] with apoptosis/necrosis [15][16][17], oxidative stress [18][19][20][21][22][23][24][25][26][27], and an exaggerated systemic inflammatory response [28][29][30]. The abnormalities observed in patients with preeclampsia include increased insulin resistance [31][32][33][34], hyperlipidemia [35][36][37], excess thrombin generation [38][39][40][41][42][43], and widespread endothelial damage/dysfunction [44][45][46] resulting in multiple organ damage.…”

Section: Introductionmentioning

confidence: 99%

Low maternal concentrations of soluble vascular endothelial growth factor receptor-2 in preeclampsia and small for gestational age

Chaiworapongsa

Romero

Gotsch

et al. 2008

The Journal of Maternal-Fetal & Neonatal Medicine

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Objectives. Preeclampsia is considered an anti-angiogenic state. A role for the anti-angiogenic factors soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and soluble endoglin in preeclampsia has been proposed. Soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) has been detected in human plasma, and the recombinant form of this protein has anti-angiogenic activity. There is a paucity of information about maternal plasma sVEGFR-2 concentrations in patients with preeclampsia and those without preeclampsia with small for gestational age (SGA) fetuses. This study was conducted to determine whether: (1) plasma sVEGFR-2 concentration changes throughout pregnancy; and (2) preeclampsia and SGA are associated with abnormalities in the maternal plasma concentration of sVEGFR-2. Study design. This cross-sectional study included non-pregnant women (n ¼ 40), women with normal pregnancies (n ¼ 135), women with an SGA fetus (n ¼ 53), and women with preeclampsia (n ¼ 112). SGA was defined as an ultrasoundestimated fetal weight below the 10 th percentile for gestational age that was confirmed by neonatal birth weight. Plasma concentrations of sVEGFR-2 were determined by ELISA. Results. (1) There was no significant difference in the mean plasma concentration of sVEGFR-2 between non-pregnant women and those with normal pregnancies ( p ¼ 0.8); (2) patients with preeclampsia and those without preeclampsia with SGA fetuses had a lower mean plasma concentration of sVEGFR-2 than that of women with normal pregnancies ( p 5 0.001 for both); and (3) there was no significant difference in the mean plasma concentration of sVEGFR-2 between patients with preeclampsia and those without preeclampsia with SGA ( p ¼ 0.9). Conclusions. Preeclampsia and SGA are associated with low plasma concentrations of sVEGFR-2. One interpretation of the findings is that plasma sVEGFR-2 concentration could reflect endothelial cell function.

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Maternal serum of women with pre-eclampsia reduces trophoblast cell viability: evidence for an increased sensitivity to Fas-mediated apoptosis

Cited by 51 publications

References 53 publications

Thrombophilic-Type Placental Pathologies and Skeletal Growth Delay Following Maternal Administration of Angiostatin4.5 in Mice

Thrombophilic-Type Placental Pathologies and Skeletal Growth Delay Following Maternal Administration of Angiostatin4.5 in Mice

Immunology of Preeclampsia

Low maternal concentrations of soluble vascular endothelial growth factor receptor-2 in preeclampsia and small for gestational age

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