Abstract
Preeclampsia is a multisystem disease that significantly contributes to maternal and fetal morbidity and mortality. In this study, we used a non-biased microarray approach to identify dysregulated genes in maternal whole blood samples which may be associated with the development of preeclampsia. Whole blood samples were obtained at 28 wk of gestation from 5 women who later developed preeclampsia (cases) and 10 matched women with normotensive pregnancies (controls). Placenta samples were obtained from an independent cohort of 19 women with preeclampsia matched with 19 women with normotensive pregnancies. We studied gene expression profiles using Illumina microarray in blood and validated changes in gene expression in whole blood and placenta tissue by qPCR. We found a transcriptional profile differentiating cases from controls; 336 genes were significantly dysregulated in blood from women who developed preeclampsia. Functional annotation of microarray results indicated that most of the genes found to be dysregulated were involved in inflammatory pathways. While general trends were preserved, only HLA-A was validated in whole blood samples from cases using qPCR (2.30- ± 0.9-fold change) whereas in placental tissue HLA-DRB1 expression was found to be significantly increased in samples from women with preeclampsia (5.88- ± 2.24-fold change). We have identified that HLA-A is upregulated in the circulation of women who went on to develop preeclampsia. In placenta of women with preeclampsia we identified that HLA-DRB1 is upregulated. Our data provide further evidence for involvement of the HLA gene family in the pathogenesis of preeclampsia.
Highlights
OF ALL PREGNANCIES worldwide, 2– 8% are affected by the severe form of spontaneous pregnancy-induced hypertension: preeclampsia [29]
Previous studies by other groups that have looked at gene expression in whole blood or peripheral blood monocytes (PBMCs) from women with preeclampsia have been analyzed in samples taken at clinical presentation [6, 30, 33] or at delivery [8, 25] and lacked translation into pregnancy-specific tissues [6, 8, 25, 30, 33]
Whole blood samples taken at 28 wk gestation were obtained in a subset of women who went on to develop preeclampsia (n ϭ 5) who were matched for age, body mass index (BMI), and parity with two normotensive women per case; these samples were subject to microarray analysis
Summary
OF ALL PREGNANCIES worldwide, 2– 8% are affected by the severe form of spontaneous pregnancy-induced hypertension: preeclampsia [29]. The fundamental changes that occur between a healthy pregnancy and the development of preeclampsia may be associated with changes in gene expression. Previous studies by other groups that have looked at gene expression in whole blood or peripheral blood monocytes (PBMCs) from women with preeclampsia have been analyzed in samples taken at clinical presentation [6, 30, 33] or at delivery [8, 25] and lacked translation into pregnancy-specific tissues [6, 8, 25, 30, 33]. We aimed to analyze gene expression patterns at a time point before clinical presentation of preeclampsia to gain insight into the pathogenic processes that are involved in the development of the condition
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