OBJECTIVE: The purpose of this study was to test the hypothesis that hypoxia down-regulates placental syncytin, which could play a role in altered placentogenesis; we investigated the influence of hypoxia on syncytin and its receptor ASCT2 gene expression in BeWo cells and in ex vivo perfused human cotyledons.STUDY DESIGN: BeWo cells were incubated with deferoxamine or cobalt chloride under normoxia and hypoxia. Additionally, a model of dually ex vivo perfused cotyledons was applied. Under hypoxic and cobalt chloride stimuli syncytin, ASCT2, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), β-actin, and β 2 -microglobulin (β 2 -MG) messenger RNAs were analyzed with the use of real-time polymerase chain reaction.RESULTS: Hypoxia, deferoxamine, and cobalt chloride markedly decreased syncytin messenger RNA in BeWo cells, whereas ASCT2 messenger RNA was not altered significantly. In isolated perfused cotyledons, hypoxia also reduced syncytin (P<.05) but not ASCT2 messenger RNA.CONCLUSION: Our data provide first evidence that syncytin gene expression is down-regulated by hypoxia, which strengthens the hypothesis that syncytin is reduced in disturbed pregnancies in the course of placental hypoxia.