Hypoxia limits differentiation and up-regulates expression and activity of prostaglandin H synthase 2 in cultured trophoblast from term human placenta.
OBJECTIVE
We determined the effect of hypoxic conditions on cellular differentiation and prostaglandin H synthase expression in cultured human term trophoblast.


METHODS
Cytotrophoblasts isolated from term placentas were cultured for 24-72 hours in a standard (20% oxygen) or hypoxic (1% to 2% oxygen) atmosphere. Trophoblast biochemical differentiation was determined by release of human chorionic gonadotropin. Morphologic differentiation was evaluated by epifluorescent and confocal microscopic examination of cultures after dual cytochemical staining for surface membrane desmosomes and intracytoplasmic nuclei. Prostaglandin H synthase 2 expression was determined by Western blot analysis and correlated with enzyme activity by immunoassay of 2 prostaglandin H synthase 2 products, prostaglandin E2 and thromboxane.


RESULTS
Human chorionic gonadotropin levels in media and syncytiotrophoblast formation were markedly diminished in trophoblast cultured in hypoxia, compared with trophoblast in control cultures, whereas viability was unchanged. Hypoxia up-regulated expression of trophoblast prostaglandin H synthase 2 but not of prostaglandin H synthase 1 and increased prostaglandin E2 and thromboxane release.


CONCLUSIONS
Hypoxia limits differentiation and enhances prostaglandin H synthase 2 expression in cultured villous trophoblast. These responses may account for the cytotrophoblast prominence characteristic of placentas exposed to attenuated oxygen delivery.
Nelson
D M
DM
Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, Missouri, USA.
Johnson
R D
RD
Smith
S D
SD
Anteby
E Y
EY
Sadovsky
Y
Y
D015153:Blotting, Western; D002454:Cell Differentiation; D015687:Cell Hypoxia; D002478:Cells, Cultured / Q000201:enzymology / Q000502:physiology; D006063:Chorionic Gonadotropin / Q000096:biosynthesis; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006801:Humans; D010920:Placenta / Q000201:enzymology / Q000502:physiology; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000201:enzymology* / Q000502:physiology*; D015854:Up-Regulation
D006063:Chorionic Gonadotropin; D013929:Thromboxane B2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone