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The Impact of Preeclampsia on Gene Expression at the Maternal-Fetal Interface.

ABSTRACT: Preeclampsia (PE) impacts 8 million mother-infant pairs worldwide each year. This human pregnancy-specific disease characterized by hypertension and proteinuria accounts for significant maternal and neonatal morbidity and mortality. The current theory of the pathogenesis of PE as reviewed by Drs. Christopher Redman and Ian Sargent is thought to occur as a 2-stage process with poor placentation in the first half of pregnancy resulting in the maternal response in the second half of pregnancy. Our studies have focused on understanding the placental contribution to this serious disease by examining the gene expression profile of the deciduas basalis or basal plate, the region of the placenta involved in the "poor placentation". In this review we present summaries of our microarray datasets both of normal placentation and those gene expression changes resulting in the context of PE. Additionally, we have taken this opportunity to combine the data sets to provide a more comprehensive view of this region of the placenta. As defects in the basal plate are, in part, at the root of the disease process, we believe that understanding the pathobiology that occurs in this region will increase our ability to alter the development and/or course of PE.

SUBMITTER: Winn VD

PROVIDER: S-EPMC3129988 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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The Impact of Preeclampsia on Gene Expression at the Maternal-Fetal Interface.

Winn Virginia D VD Gormley Matthew M Fisher Susan J SJ

Pregnancy hypertension 20110101 1

Preeclampsia (PE) impacts 8 million mother-infant pairs worldwide each year. This human pregnancy-specific disease characterized by hypertension and proteinuria accounts for significant maternal and neonatal morbidity and mortality. The current theory of the pathogenesis of PE as reviewed by Drs. Christopher Redman and Ian Sargent is thought to occur as a 2-stage process with poor placentation in the first half of pregnancy resulting in the maternal response in the second half of pregnancy. Our ...[more]

PMID: 21743843

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Project description:Preeclampsia (PE), which affects 4-8% of human pregnancies, causes significant maternal and neonatal morbidity and mortality. Within the basal plate, placental cytotrophoblasts (CTBs) of fetal origin invade the uterus and extensively remodel the maternal vasculature. In PE, CTB invasion is often shallow, and vascular remodeling is rudimentary. To better understand possible causes, we conducted a global analysis of gene expression at the maternal-fetal interface in placental samples from women with PE (n = 12; 24-36 wk) vs. samples from women who delivered due to preterm labor with no evidence of infection (n = 11; 24-36 wk), a condition that our previous work showed is associated with normal CTB invasion. Using the HG-U133A&B Affymetrix GeneChip platform, and statistical significance set at log odds-ratio of B >0, 55 genes were differentially expressed in PE. They encoded proteins previously associated with PE [e.g. Flt-1 (vascular endothelial growth factor receptor-1), leptin, CRH, and inhibin] and novel molecules [e.g. sialic acid binding Ig-like lectin 6 (Siglec-6), a potential leptin receptor, and pappalysin-2 (PAPP-A2), a protease that cleaves IGF-binding proteins]. We used quantitative PCR to validate the expression patterns of a subset of the genes. At the protein level, we confirmed PE-related changes in the expression of Siglec-6 and PAPP-A2, which localized to invasive CTBs and syncytiotrophoblasts. Notably, Siglec-6 placental expression is uniquely human, as is spontaneous PE. The functional significance of these novel observations may provide new insights into the pathogenesis of PE, and assaying the circulating levels of these proteins could have clinical utility for predicting and/or diagnosing PE. Keywords: disease state analysis Basal plate biopsies of preterm labor (24-36 weeks; n=11) and preterm severe preeclampsia (24-36 weeeks; n=12) were isolated and the global gene expression profiles determined using Affymetrix Human GeneChips. Comparisons between the preeclampsia samples and the preterm labor controls revealed genes differentially expressed in preeclampsia.

Project description:Background and objectiveThe establishment of maternal-fetal interface immune tolerance is essential for successful pregnancy. Studies have shown that spontaneous abortion, recurrent abortion, and fetal growth restriction are related to maternal-fetal interface immune dysfunction. Preeclampsia is an idiopathic condition related to pregnancy which manifests as hypertension, proteinuria, and other target organ damage after 20 weeks of gestation. Although the etiology of preeclampsia is still unknown, its pathogenesis is thought to be related to genetics, environment, and metabolism. In recent years, more and more studies have been conducted on the mechanism of immune tolerance at the maternal-fetal interface and the relationship between immune dysregulation and the pathogenesis of preeclampsia. This paper summarizes the latest studies on this topic in order to find new insights into the pathogenesis of preeclampsia and make a reflection on clinical diagnosis and treatment in different phenotype of preeclampsia.MethodsThe research and latest progress published from 2000 to December 2021 on the relationship between maternal-fetal interface immune tolerance and preeclampsia were broadly retrieved and researched using PubMed and Web of Science databases.Key content and findingsThe mechanism of natural killer cells (NK cells) and macrophages at the maternal-fetal interface in immune tolerance, as well as their cytotoxicity and cytokine secretion dysfunction, may be related to the pathogenesis of preeclampsia. The expression of nonclassical type I human leukocyte antigen (HLA) on extravillous trophoblast (EVT) cell were down-regulated in decidua of preeclampsia, which may induce increase EVT death caused by activating of cytotoxic NK cell. In addition, genetic polymorphism of nonclassical type I HLA on the EVT cell membrane may be related to the pathogenesis of preeclampsia, although this is likely to be a combination of 3 nonclassical type I HLA genotypes and requires sequencing to verify.ConclusionsWe demonstrated how the maternal-fetal interface immune dysfunction contribute to the pathogenesis of preeclampsia, further study and clinical trial based on this theory of pathogenesis may reveal new immune treatment method of preeclampsia.

Dataset Information

The Impact of Preeclampsia on Gene Expression at the Maternal-Fetal Interface.

Publications

The Impact of Preeclampsia on Gene Expression at the Maternal-Fetal Interface.

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