Hypoxia Represses the Differentiation of Rcho-1 Rat Trophoblast Giant Cells

Abstract

Background: A hypoxic environment is known to be essential for early placentation. A low oxygen tension induces hypoxia-inducible factor-1 (HIF-1α) 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-1α, caused downregulation of Id-1 transcription factor and trophoblast giant cell differentiation. Conclusion: These results indicate that hypoxia represses rat trophoblast giant cell differentiation via an HIF-1α-independent pathway.