Hypoxia Upregulates GCM1 in Human Placenta Explants

Studies in mice have shown that a variety of genes, including GCM1, regulate the differentiation of trophoblast cells. GCM1 is also expressed in the human placenta. Placental GCM1 protein has been reported to be reduced in preeclampsia. In view of the close link between hypoxia, hypoxia-reoxygenation, preeclampsia, placental development and the reported reduction in GCM1, we hypothesised that GCM1 expression would be affected by hypoxia. The aim was to determine the effects of hypoxia on GCM1 expression in the human placenta. Two model systems were used; villous explants and cultured primary cytotrophoblast cells. GCM1 protein was detectable at low levels in explants maintained for 7 h in 8 or 20% O-2. A striking increase in GCM1 was observed when villous explants were incubated for 1h in 1% O-2 (p < 0.002). Incubation of explants for 1 h in 1% O-2 followed by re-oxygenation for 6 h in 8 or 20% O-2 resulted in a decline in GCM1 protein. Expression of GCM1 was also analysed in primary cytotrophoblast and syncytiotrophoblast cultured in 8 or 20% O-2 or reduced oxygen (1-2% O-2) conditions. GCM1 protein was not detected in any of the experimental conditions used. This study has shown that acute hypoxia increases GCM-1 protein in villous explants. The experiments with purified trophoblast do not support a role for hypoxia increasing GCM-1 in these cells under the conditions used. The present findings are in keeping with the complex effects of oxygen depending on the conditions used. The hypoxic effects on GCM1 warrant further investigation as they may provide further information on the pathogenesis of preeclampsia.