Hypoxia represses the differentiation of Rcho-1 rat trophoblast giant cells.
BACKGROUND
A hypoxic environment is known to be essential for early placentation. A low oxygen tension induces hypoxia-inducible factor-1 (HIF-1alpha) which may play an important role as a transcription factor in maintaining the proliferative and undifferentiated phenotype in human trophoblasts.


METHODS
We analyzed the effect of a low oxygen tension on the rat trophoblast giant cell differentiation pathway using Rcho-1 cells which were derived from rat choriocarcinomas and consist of trophoblast stem cells.


RESULTS
We found that a low oxygen tension suppressed the morphological changes and steroidogenesis during differentiation. The anticipated downregulation of the Id-1 transcription factor, a negative regulator of trophoblast giant cell differentiation, was not observed in the hypoxic environment. On the other hand, deferoxamine, which mimics hypoxia and induces HIF-1alpha, caused downregulation of Id-1 transcription factor and trophoblast giant cell differentiation.


CONCLUSIONS
These results indicate that hypoxia represses rat trophoblast giant cell differentiation via an HIF-1alpha-independent pathway.
Takeda
Takashi
T
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan. take@gyne.med.osaka-u.ac.jp
Sakata
Masahiro
M
Isobe
Aki
A
Yamamoto
Toshiya
T
Nishimoto
Fumihito
F
Minekawa
Ryoko
R
Okamoto
Yoko
Y
Tasaka
Keiichi
K
Murata
Yuji
Y
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D000860:Hypoxia; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D051381:Rats; D014327:Trophoblasts / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D051793:Hypoxia-Inducible Factor 1