Differential Placental Gene Expression in Severe Preeclampsia

Sitras, V.; Paulssen, R.H.; Grønaas, H.; Leirvik, J.; Hanssen, T.A.; Vårtun, Å.; Acharya, G.

doi:10.1016/j.placenta.2009.01.012

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Volume 30, Issue 5 , Pages 424-433, May 2009

Differential Placental Gene Expression in Severe Preeclampsia

V. Sitras
- Department of Obstetrics and Gynecology, University Hospital of Northern Norway and Institute of Clinical Medicine, University of Tromsø, PO Box 24, N-9038 Tromsø, Norway
- Corresponding author. Tel.: +47 776 26 000; fax: +47 776 26 421.
- These authors contributed equally to this work.
R.H. Paulssen
- Laboratory of Molecular Medical Research, Institute of Clinical Medicine, University of Tromsø, N-9037, Norway
- These authors contributed equally to this work.
H. Grønaas
- Department of Medical Genetics, University Hospital of Northern Norway, N-9038, Norway
- Present address: WesternGeco, Oslo Technology Center, Schlumberger House, N-1372 Asker, Norway.
J. Leirvik
- Department of Medical Genetics, University Hospital of Northern Norway, N-9038, Norway
T.A. Hanssen
- Department of Pathology, University Hospital of Northern Norway, N-9038, Norway
Å. Vårtun
- Department of Obstetrics and Gynecology, University Hospital of Northern Norway and Institute of Clinical Medicine, University of Tromsø, PO Box 24, N-9038 Tromsø, Norway
G. Acharya
- Department of Obstetrics and Gynecology, University Hospital of Northern Norway and Institute of Clinical Medicine, University of Tromsø, PO Box 24, N-9038 Tromsø, Norway

Accepted 28 January 2009. published online 02 March 2009.

Abstract

We investigated the global placental gene expression profile in severe preeclampsia. Twenty-one women were randomly selected from 50 participants with uncomplicated pregnancies to match 21 patients with severe preeclampsia. A 30K Human Genome Survey Microarray v.2.0 (Applied Biosystems) was used to evaluate the gene expression profile. After RNA isolation, five preeclamptic placentas were excluded due to poor RNA quality. The series composed of 37 hybridizations in a one-channel detection system of chemiluminescence emitted by the microarrays. An empirical Bayes analysis was applied to find differentially expressed genes. In preeclamptic placentas 213 genes were significantly (fold-change≥2 and p≤0.01) up-regulated and 82 were down-regulated, compared with normal placentas. Leptin (40 fold), laeverin (10 fold), different isoforms of β-hCG (3–6 fold), endoglin (4 fold), FLT1 (3 fold) and FLT4 (2 fold) were up-regulated. PDGFD was down-regulated (2 fold). Several differentially expressed genes were associated with Alzheimer disease, angiogenesis, Notch-, TGFβ- and VEGF-signalling pathways. Sixteen genes best discriminated preeclamptic from normal placentas. Comparison between early- (<34 weeks) and late-onset preeclampsia showed 168 differentially expressed genes with oxidative stress, inflammation, and endothelin signalling pathways mainly involved in early-onset disease. Validation of the microarray results was performed by RT-PCR, quantitative urine hCG measurement and placental histopathologic examination. In summary, placental gene expression is altered in preeclampsia and we provide a comprehensive list of the differentially expressed genes. Placental gene expression is different between early- and late-onset preeclampsia, suggesting differences in pathophysiology.