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Molecular Evidence of Placental Hypoxia in Preeclampsia

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TLDR
The results provide molecular evidence that aberrant global placental gene expression changes in preeclampsia may be due to reduced oxygenation and that these events can successfully be mimicked by in vivo and in vitro models of placental hypoxia.
Abstract
Background: Oxygen plays a central role in human placental pathologies including preeclampsia, a leading cause of fetal and maternal death and morbidity. Insufficient uteroplacental oxygenation in preeclampsia is believed to be responsible for the molecular events leading to the clinical manifestations of this disease. Design: Using high-throughput functional genomics, we determined the global gene expression profiles of placentae from high altitude pregnancies, a natural in vivo model of chronic hypoxia, as well as that of first-trimester explants under 3 and 20% oxygen, an in vitro organ culture model. We next compared the genomic profile from these two models with that obtained from pregnancies complicated by preeclampsia. Microarray data were analyzed using the binary tree-structured vector quantization algorithm, which generates global gene expression maps. Results: Our results highlight a striking global gene expression similarity between 3% O2-treated explants, high-altitude placentae, and importan...

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Journal ArticleDOI

Preeclampsia: Pathophysiology, Challenges, and Perspectives

TL;DR: The current evidence for the role of abnormal placentation and therole of placental factors such as the antiangiogenic factor, sFLT1 (soluble fms-like tyrosine kinase 1) in the pathogenesis of the maternal syndrome of preeclampsia is discussed.
Journal ArticleDOI

Pathogenesis of Preeclampsia

TL;DR: The recent discoveries of upregulated antiangiogenic factors provide promise for future testing to predict and diagnose preeclampsia as well as therapeutic targets for amelioration of the clinical disease.
Journal ArticleDOI

Gene expression patterns in human placenta

TL;DR: This study provides a rich and diverse picture of the molecular variation in the placenta from healthy pregnancies and identifies sets of genes whose expression in Placenta was significantly correlated with the sex of the fetus.
Journal ArticleDOI

Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases

TL;DR: The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular reactive oxygen species (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive as discussed by the authors.
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Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

TL;DR: It is argued that the role of poorly liganded iron has been rather underappreciated in the past, and that in combination with peroxide and superoxide its activity underpins the behaviour of a great many physiological processes that degrade over time.
References
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Journal ArticleDOI

Analysis of relative gene expression data using real-time quantitative pcr and the 2(-delta delta c(t)) method

TL;DR: The 2-Delta Delta C(T) method as mentioned in this paper was proposed to analyze the relative changes in gene expression from real-time quantitative PCR experiments, and it has been shown to be useful in the analysis of realtime, quantitative PCR data.
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Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1.

TL;DR: HIF-1 is implicate in the activation of VEGF transcription in hypoxic cells and this work demonstrates the involvement of Hif-1 in theactivation of V EGF transcription.
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Circulating Angiogenic Factors and the Risk of Preeclampsia

TL;DR: Alterations in the levels of sFlt-1 and free PlGF were greater in women with an earlier onset of preeclampsia and in women in whom preeClampsia was associated with a small-for-gestational-age infant.
Journal ArticleDOI

Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies

TL;DR: Factors that may be present at antenatal booking and the underlying evidence base can be used to assess risk at booking so that a suitable surveillance routine to detect pre-eclampsia can be planned for the rest of the pregnancy.
Journal ArticleDOI

Pathogenesis and genetics of pre-eclampsia.

TL;DR: There are genetic components to susceptibility, but the relative contributions of maternal and fetal genotypes are still unclear and whole-genome mapping could ultimately define the causative genes.
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