Tumor suppressor and growth regulatory genes are overexpressed in severe early-onset preeclampsia--an array study on case-specific human preeclamptic placental tissue.

BACKGROUND: Preeclampsia is an important clinical condition with unknown etiology. We used DNA array technique to compare placental gene expression profile in severe early-onset preeclampsia from 25 to 27 gestational weeks with strictly non-affected placental samples from similar gestational weeks. METHOD: DNA arrays were validated by showing the up-regulation of several genes typical for preeclampsia such as chorionic gonadotrophin beta-chain, tissue factor pathway inhibitor, and intercellular adhesion molecule-1. In DNA array, 5% of genes displayed less than or equal to twofold increase in expression level and only 0.2% of genes showed < or =0.5-fold decrease in expression in preeclampsia versus control. Signs of immunological factors, hypoxia, apoptosis, oxidative stress and altered thrombosis, coagulation as well as endothelial injury were seen in the gene expression profile. RESULTS: As a new finding, we identified a group of 13 genes with a function in tumor suppression and growth regulation which were significantly up-regulated in preeclampsia. Three out of the five most highly up-regulated genes belonged to this group which included genes, such as protein phosphatase 2, phospholipid scramblase 1, transcription elongation factor, melanoma adhesion molecule, retinoic acid receptor responder 3, and RANTES. CONCLUSIONS: It is concluded that up-regulation of tumor suppressor and growth regulatory genes may play an important role in the pathogenesis of severe early-onset preeclampsia.

Fetal membranes act as a barrier for adenoviruses: gene transfer into exocoelomic cavity of rat fetuses does not affect cells in the fetus.

OBJECTIVES: In utero gene therapy has a potential to correct genetic disorders before the first clinical symptoms appear. Our aim was to examine whether the exocoelomic cavity between amniotic and chorionic membranes offers a minimally invasive route for gene transfer to the fetus during early pregnancy. STUDY DESIGN: We injected lacZ-adenovirus (4 x 10(9) pfu) during open surgery into the exocoelomic cavity of rat fetuses (n=50) and analyzed the fetuses and rat dams for transgene expression with X-gal staining and polymerase chain reaction. RESULTS: Giant cells around Reichert's membrane, the outermost extraembryonic membrane in rodents, were transduced; but no transduction was observed in the cells of the fetuses or rat dams. CONCLUSION: In rodents, the exocoelomic cavity does not offer a route for gene transfer into the fetus. It was concluded that fetal membranes act as a barrier that prevents adenoviral particles from passing between embryonic cavities.

Gene transfer to human placenta ex vivo: a novel application of dual perfusion of human placental cotyledon.

OBJECTIVE: The purpose of this study was to determine whether the transfer of a marker gene in dual recirculating human placental perfusion is feasible and whether the transgene production is detectable by X-Gal histochemistry. STUDY DESIGN: Four term human placentas were perfused for 9 to 16 hours in a dual perfusion chamber. At the beginning of each experiment, an adenoviral vector that carried beta-galactosidase gene was added to the maternal perfusate that was entering the intervillous space; at the end, the placental tissues were analyzed for beta-galactosidase activity by X-Gal staining. RESULTS: Adenovirus-mediated gene transfer resulted in a 0.5% to 1% gene transfer efficiency in placental trophoblastic cells after 9 hours of perfusion, whereas the gene transfer efficiency was much higher, to 5% after 16 hours of perfusion. When postperfusion tissue explant cultures were analyzed for beta-galactosidase expression 56 hours after the perfusion, the transfection rate was as high as 11%. CONCLUSION: Perfused human placenta can be efficiently transfected with adenoviral vectors, and the expression of the transgene can be detected in the trophoblastic cells. This system can be used for the optimization and analysis of gene transfer conditions to human placenta without any risk to the fetus.