Article

Altered Global Gene Expression in First Trimester Placentas of Women Destined to Develop Preeclampsia

School of Nursing, Department of Health Promotion and Development, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Placenta (Impact Factor: 2.71). 12/2008; 30(1):15-24. DOI: 10.1016/j.placenta.2008.09.015
Source: PubMed

ABSTRACT

Preeclampsia is a pregnancy-specific disorder that remains a leading cause of maternal, fetal and neonatal morbidity and mortality, and is associated with risk for future cardiovascular disease. There are no reliable predictors, specific preventative measures or treatments other than delivery. A widely held view is that the antecedents of preeclampsia lie with impaired placentation in early pregnancy. Accordingly, we hypothesized dysregulation of global gene expression in first trimester placentas of women who later manifested preeclampsia.
Surplus chorionic villus sampling (CVS) tissues were collected at 10-12 weeks gestation in 160 patients with singleton fetuses. Four patients developed preeclampsia, and their banked CVS specimens were matched to 8 control samples from patients with unaffected pregnancies. Affymetrix HG-U133 Plus 2.0 GeneChips were utilized for microarray analysis. Naïve Bayes prediction modeling and pathway analysis were conducted. qRT-PCR examined three of the dysregulated genes.
Thirty-six differentially expressed genes were identified in the preeclampsia placentas. qRT-PCR verified the microarray analysis. Thirty-one genes were down-regulated. Many were related to inflammation/immunoregulation and cell motility. Decidual gene dysregulation was prominent. No evidence was found for alterations in hypoxia and oxidative stress regulated genes.
To our knowledge, this is the first study to show dysregulation of gene expression in the early placentas of women approximately 6 months before developing preeclampsia, thereby reinforcing a placental origin of the disorder. We hypothesize that placentation in preeclampsia is compromised in the first trimester by maternal and fetal immune dysregulation, abnormal decidualization, or both, thereby impairing trophoblast invasion. Several of the genes provide potential targets for the development of clinical biomarkers in maternal blood during the first trimester. Supplementary materials are available for this article via the publisher's online edition.

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    • "Differential gene expression was examined by Illumina Mouse WG-6 v2.0 Expression Bead Chip microarray analysis. The extraembryonic trophectoderm-derived tissues (chorion, ectoplacental cone and giant cell layer) at E7.5 and the visually identified placentas at E9.5 were separated from embryonic tissue and maternal uterus tissue.The publicly available human placenta data were downloaded from GEO under accession numbers GSE9984, GSE12767 and GSE7434 (Huuskonen et al., 2008;Mikheev et al., 2008;Founds et al., 2009). For details of the microarray and data analysis, see the supplementary material methods. "
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    • "Whilst the clinical manifestations of pre-eclampsia occur in late pregnancy, the molecular events leading into the onset of this disease are thought to originate in early pregnancy [1]. In support of this, global alterations in the expression of genes related to inflammation/immunoregulation and cell motility were found in the placenta of first trimester women that subsequently developed pre-eclampsia [4], which has re-enforced the concept of a placental origin of the disorder. As a result, it is generally accepted that pre-eclampsia occurs secondary to insufficient placentation (development of the placenta) [5] [6]. "
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