Oxygen tension modulates AQP9 expression in human placenta

Placental hypoxia has been implicated in pregnancy pathologies such as preeclampsia. We have previously reported that AQP9 is highly expressed in syncytiotrophoblast from normal placentas and shows an overexpression in preeclamptic placentas, with a lack of functionality for water transport. Up to now, the response of AQP9 to changes in the oxygen tension in trophoblast cells is still unknown. Objective: Our aim was to establish whether alterations in oxygen levels may modulate AQP9 expression in human placenta. Methods: A theoretical analysis of the human AQP9 gene to find conserved DNA regions that could serve as putative HIF-1 binding sites. Then, explants from normal placentas were cultured at different concentrations of oxygen or with 250 mu M CoCl2. AQP9 molecular expression and water uptake was determined. Results: Fourteen consensus HIF-1 binding sites were found in the human AQP9 gene, but none of them in the promoter region. However, placental AQP9 decreased abruptly when HIF-1 alpha is expressed by deprivation of oxygen or CoCl2 stabilization. In contrast, after reoxygenation, HIF-1 alpha was undetectable while AQP9 increased significantly and changed its cellular distribution, showing the same pattern as that previously described in preeclamptic placentas. Accordingly with the decrease in AQP9 expression, water uptake decreased in explants exposed to hypoxia or treated with CoCl2. Conversely as we expected, after reoxygenation, water uptake decreased dramatically compared to the control and was not sensitive to HgCl2. Conclusion: Our findings suggest that oxygen tension may modulate AQP9 expression in human placenta. However, the role of AQP9 still remains uncertain. (c) 2013 Elsevier Ltd. All rights reserved.