Circulating Fetal DNA in Maternal Plasma Is Increased in Pregnancies at High Altitude and Is Further Enhanced by Preeclampsia

Zhong, Xiao Yan; Wang, Yiming; Chen, Su-Qin; Labu,; Pubuzhuoma,; Gesangzhuogab,; Ouzhuwangmu,; Pan, Xiaoying; Zhu, Ninghu; Hahn, Chin‐Lo; Huppertz, Berthold; Holzgreve, Wolfgang; Hahn, Sinuhe

doi:10.1373/clinchem.2004.041806

Cited by 21 publications

(12 citation statements)

References 15 publications

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“…Although others have investigated the association of placental debris with endothelial function [32][33][34], our objective was to relate maternal plasma levels of fetal CRH mRNA and PS-exposing microparticles to markers of coagulation activation in addition to those of endothelial activation. It is not yet clear whether elevated maternal plasma levels of fetal mRNA or DNA are specific to pre-eclampsia or may also be observed in intrauterine growth restriction [35,36], but increased levels are observed in high-altitude pregnancies [37]. Bretelle et al [15] found no difference in total annexin V-positive microparticles or procoagulant activity between healthy and growthrestricted pregnancies.…”

Section: Discussionmentioning

confidence: 99%

Fetal corticotrophin-releasing hormone mRNA, but not phosphatidylserine-exposing microparticles, in maternal plasma are associated with factor VII activity in pre-eclampsia

Freeman¹,

Tham²,

Ea³

et al. 2008

Journal of Thrombosis and Haemostasis

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To cite this article: Freeman DJ, Tham K, Brown EA, Rumley A, Lowe GD, Greer IA. Fetal corticotrophin-releasing hormone mRNA, but not phosphatidylserine-exposing microparticles, in maternal plasma are associated with factor VII activity in pre-eclampsia. J Thromb Haemost 2008; 6: 421-7Summary. Background: Pre-eclampsia is associated with increased placental debris circulating in maternal plasma. Objectives: This study related placental debris to maternal markers of coagulation and endothelial activation in pre-eclampsia. Patients/methods: Circulating fetal corticotrophin-releasing hormone (CRH) mRNA and phosphatidylserine (PS)-exposing microparticles were assayed in third trimester plasma from women with pre-eclampsia (n = 32) and controls (n = 32) matched for age, body mass index, parity, and gestational age at sampling. Markers of maternal hemostasis and endothelial function were assessed. Results: Fetal CRH mRNA levels were higher in pre-eclampsia [mean 0.75 (SD 2.77) CRH/glyceraldehyde-3-phosphate dehydrogenase (GAP-DH) mRNA ratio] than in control pregnancies [0.20 (0.74), P = 0.014]. PS-exposing microparticle levels were not different between the groups. Women with pre-eclampsia had higher levels of tissue factor pathway inhibitor (TFPI), prothrombin F 1+2 fragment (F 1+2 ), factor XIIa, soluble vascular cell adhesion molecule 1, von Willebrand factor and plasminogen activator inhibitor 1 than controls. Fetal CRH mRNA correlated with TFPI in pre-eclampsia and control groups (r = 0.38, P = 0.031, and r = 0.37, P = 0.039, respectively). Fetal CRH mRNA correlated with FVII activity (r = 0.43, P = 0.017) and PS-exposing microparticles correlated inversely with F 1+2 (r = )0.64, P < 0.001) in preeclampsia. Conclusions: Placental debris, assessed by fetal CRH mRNA levels in maternal blood, is related to coagulation potential, i.e. FVII activity, but not to markers of coagulation or endothelial activation in pre-eclampsia.

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Section: Discussionmentioning

confidence: 99%

Fetal corticotrophin-releasing hormone mRNA, but not phosphatidylserine-exposing microparticles, in maternal plasma are associated with factor VII activity in pre-eclampsia

Freeman¹,

Tham²,

Ea³

et al. 2008

Journal of Thrombosis and Haemostasis

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“…Blood samples were centrifuged at 2,500 g for 10 min. Serum and plasma were aliquoted after recentrifugation (12,000 g for 5 min) and stored at -80°C until further analysis as carried out previously [7,11,12,13,14,15]. …”

Section: Methodsmentioning

confidence: 99%

Elevated Levels of Total Cell-Free DNA in Maternal Serum Samples Arise from the Generation of Neutrophil Extracellular Traps

et al. 2016

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Introduction: The analysis of cell-free DNA from maternal blood samples has facilitated the noninvasive detection of fetal aneuploidies or hereditary Mendelian disorders. In this context, previous studies have indicated that the pool of cell-free DNA is greater in maternal serum than in plasma samples, necessitating optimized collection and storage protocols. As the source of this increased amount of cell-free DNA is not clear, we have now examined whether neutrophil extracellular traps (NETs) contribute to this material. Material and Methods: Serum samples were collected in all three trimesters of normal healthy pregnant women, and at term from cases with manifest preeclampsia. The presence of NET-derived material was demonstrated by the detection of cell-free DNA fragments complexed to neutrophil granular proteins (i.e. myeloperoxidase). Results: Our data indicate that NET-derived cell-free DNA/myeloperoxidase complexes were greater in serum from normal pregnant women than in normal matching nonpregnant controls. This neutrophil chromosomal material increased incrementally throughout gestation and was most pronounced in cases with preeclampsia. Discussion: By detecting increased levels of cell-free DNA/myeloperoxidase complexes in maternal serum samples, our data indicate that a significant proportion of this material is derived from the generation of NETs.

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“…In support of this idea, women with preeclampsia exhibit increased shedding of not only trophoblast cells in the maternal circulation (37,38), but also circulating syncytiotrophoblast membrane (STMB) fragments (39), cytokeratin 18 intermediate filaments typical of the trophoblast epithelium (40), and fetal DNA and RNA in syncytiotrophoblast micro particles (41)(42)(43). Again suggesting a role for hypoxia, fetal DNA derived from syncytiotrophoblast particles is increased in pregnancies exposed to hypoxia because of residence at high altitude, compared to women at sea level (44). Such micro-particles are identified in even higher numbers in pregnant women at high altitude who develop preeclampsia (44).…”

Section: Necrosis Trophoblast Debris and Preeclampsiamentioning

confidence: 95%

Trophoblast biology, responses to hypoxia and placental dysfunction in preeclampsia

Rampersad¹

2007

Front Biosci

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Preeclampsia is a hypertensive disorder unique to human pregnancy that can result in significant morbidity and mortality for mother and fetus. While the etiology of preeclampsia is unknown, the placenta in general and trophoblast in particular is a prerequisite for the disease. We overview normal development of the human placenta, describe the role of hypoxia and other insults in placental injury, and highlight how the dysregulation of villous trophoblast biology in the second half of pregnancy may incite the pathophysiology of preeclampsia in the mother.

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Circulating Fetal DNA in Maternal Plasma Is Increased in Pregnancies at High Altitude and Is Further Enhanced by Preeclampsia

Cited by 21 publications

References 15 publications

Fetal corticotrophin-releasing hormone mRNA, but not phosphatidylserine-exposing microparticles, in maternal plasma are associated with factor VII activity in pre-eclampsia

Fetal corticotrophin-releasing hormone mRNA, but not phosphatidylserine-exposing microparticles, in maternal plasma are associated with factor VII activity in pre-eclampsia

Elevated Levels of Total Cell-Free DNA in Maternal Serum Samples Arise from the Generation of Neutrophil Extracellular Traps

Trophoblast biology, responses to hypoxia and placental dysfunction in preeclampsia

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