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Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-0078
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The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 7 4299-4308
Copyright © 2005 by The Endocrine Society

Molecular Evidence of Placental Hypoxia in Preeclampsia

Nima Soleymanlou, Igor Jurisica, Ori Nevo, Francesca Ietta, Xin Zhang, Stacy Zamudio, Martin Post and Isabella Caniggia

Department of Obstetrics and Gynecology (I.C., O.N.), Mount Sinai Hospital (I.C., N.S., O.N., F.I.), Toronto, Canada M5G 1X5; Department of Pediatrics (M.P., I.C.), The Hospital for Sick Children (M.P., N.S.), Toronto, Canada M5G 1X8; Departments of Physiology (M.P., N.S., I.C.) and Medical Biophysics and Computer Science (I.J.), Ontario Cancer Institute, Princess Margaret Hospital (I.J., X.Z.), Toronto, Ontario, Canada M5G 2M9; University of Toronto (I.C., M.P., N.S., I.J.), Toronto, Ontario, Canada M5S 1A1; and New Jersey Medical School (S.Z.)., Newark, New Jersey 07101-1709

Address all correspondence and requests for reprints to: Isabella Caniggia, M.D., Ph.D., Mount Sinai Hospital, Samuel Lunenfeld Research Institute, 600 University Avenue, Room 871, Toronto, Ontario, Canada M5G 1X5. E-mail: caniggia{at}mshri.on.ca.

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.

Design: 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% O2-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.

Conclusion: 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.




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