Molecular evidence of placental hypoxia in preeclampsia.
BACKGROUND
Oxygen plays a central role in human placental pathologies including preeclampsia, a leading cause of fetal and maternal death and morbidity. Insufficient uteroplacental oxygenation in preeclampsia is believed to be responsible for the molecular events leading to the clinical manifestations of this disease.


METHODS
Using high-throughput functional genomics, we determined the global gene expression profiles of placentae from high altitude pregnancies, a natural in vivo model of chronic hypoxia, as well as that of first-trimester explants under 3 and 20% oxygen, an in vitro organ culture model. We next compared the genomic profile from these two models with that obtained from pregnancies complicated by preeclampsia. Microarray data were analyzed using the binary tree-structured vector quantization algorithm, which generates global gene expression maps.


RESULTS
Our results highlight a striking global gene expression similarity between 3% O(2)-treated explants, high-altitude placentae, and importantly placentae from preeclamptic pregnancies. We demonstrate herein the utility of explant culture and high-altitude placenta as biologically relevant and powerful models for studying the oxygen-mediated events in preeclampsia.


CONCLUSIONS
Our results provide molecular evidence that aberrant global placental gene expression changes in preeclampsia may be due to reduced oxygenation and that these events can successfully be mimicked by in vivo and in vitro models of placental hypoxia.
Soleymanlou
Nima
N
Department of Obstetrics and Gynecology, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
Jurisica
Igor
I
Nevo
Ori
O
Ietta
Francesca
F
Zhang
Xin
X
Zamudio
Stacy
S
Post
Martin
M
Caniggia
Isabella
I
D000328:Adult; D000465:Algorithms; D000531:Altitude; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D042461:Vascular Endothelial Growth Factor A