First-trimester trophoblast cell model gene response to hypoxia.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Koklanaris
Nikki
N
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA. koklan01@med.nyu.edu
Nwachukwu
Jerome C
JC
Huang
S Joseph
SJ
Guller
Seth
S
Karpisheva
Ksenia
K
Garabedian
Michael
M
Lee
Men-Jean
MJ
D015687:Cell Hypoxia / Q000235:genetics*; D002460:Cell Line; D005260:Female; D006801:Humans; D046228:Microarray Analysis; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000166:cytology*