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Am J Obstet Gynecol. 2006 Mar;194(3):687-93.

First-trimester trophoblast cell model gene response to hypoxia.

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  • 1Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA.



Trophoblast invasion, which sets the stage for placentation and pregnancy outcome, likely occurs in a hypoxic environment. We used microarray technology in a trophoblast cell line to identify hypoxia-responsive genes that may impact placentation.


An immortalized extravillous cytotrophoblast cell line, HTR-8/SVneo, was exposed to normoxia (20% oxygen) or hypoxia (1% oxygen) for 6 hours. Total RNA was harvested and prepared for microarray study. Quantitative reverse transcriptase polymerase chain reaction was performed for array confirmation.


We confirmed the up- and down-regulation of 10 hypoxia-responsive genes using quantitative reverse transcriptase polymerase chain reaction. Ontologic gene categories that were found to be hypoxia-responsive included motility/migration, angiogenesis, and apoptosis.


Specific genes that were found to be up-regulated in this first-trimester array (such as plasminogen activator inhibitor-1 and tissue inhibitor of metalloproteinase 3) have been described in preeclampsia. The hypoxia-responsive genes that we identified may be physiologic in early pregnancy. However, up-regulation of these same genes in later pregnancy augurs poorly.

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