Targeted gene analysis in preeclamptic placentas

Preeclampsia (PE) is characterized by new onset of hypertension and proteinuria in the second half of gestation. It is one of the leading causes of maternal and fetal morbidity and mortality. Despite intensive research, however, the molecular mechanisms have not well defined. Microarray-based transcriptional profiling has been widely used for identifying placental genes responsible for PE. We have constructed gene arrays containing most important genes coding for molecules involved in critical signaling transduction pathways in PE and analyzed placental samples from preeclampsia patients and controls. The results were corroborated by QT-PCR and Western blot analysis. We show that genes associated with angiogenesis and migration pathway are mostly altered. Interestingly, beside known genes, we have identified novel genes associated with preeclampsia, such as BCL6 (B-cell lymphoma), SURVIVIN, RAC1 and CAVEOLIN 2. The SURVIVIN gene is reduced but the protein is hardly changed in preeclampsia placentas compared to control. Upon stress, survivin in trophoblastic cells is phosphorylated and becomes stabilized. Depletion of SURVIVIN inhibits proliferation and induces chromosome misalignment and abnormal centrosome integrity. On the other hand, BCL6 gene as well as protein expression is increased in preeclampsia placentas compared to controls. It remains to be defined what kind of roles of deregulated BCL6 in the development of preeclampsia. Taken together, our data show that targeted gene analysis could effectively corroborate and identify genes and pathways deregulated in preeclampsia. In particular, altered expression of BCL6 and SURVIVIN could be linked to the disease.