Water Channel Proteins in the Human Placenta.

DAMIANO ALICIA E

Santiago

Congreso; International Federation of Placenta Associations Meeting; 2010

International Federation of Placenta Associations

In many tissues, water channel proteins known as aquaporins (AQPs) have been implicated in transmembrane water transport. Previous research suggested that water movement across human syncytiotrophoblast (hST) should take place by a lipid diffusion pathway. However, in 2001 we reported that aquaporin-9 (AQP9) and 3 (AQP3) are highly expressed in hST from normal placenta. However, up to now, the physiological function(s) and the regulation of human placental AQPs remain unknown.We also reported that AQP9 protein expression was increased in preeclamptic placentas while AQP3 was decreased. However, we could not relate the higher AQP9 expression with its functionality for the transport of water and mannitol. Thus, we were focused on establishing the mechanisms that may modulate AQP3 and AQP9 expression and functionality. In placental explants cultured under hypoxia conditions we demonstrated that changes in oxygen tension may be responsible for the dysregulation of both proteins. In addition, insulin treatment decreased AQP9 but had no effect on AQP3 expression.On the other hand, we studied hST membranes lipid composition and observed that the apical membrane fluidity was reduced in preeclamptic placentas. Furthermore, recently we found that CFTR expression was almost undetectable in preeclamptic placentas and failed to regulate AQPs activity suggesting that CFTR may be involved in the regulation of transcellular water flux in human placentas. In conclusion, our finding suggested that in preeclamptic placentas insulin was not effective to down-regulate AQP9 expression, although AQP9 gen has a negative insulin-response-element, and the intermittent hypoxia contribute synergistically to its up-regulation. In contrast, AQP3 decrease may be only caused by changes in oxygen tension. Our results also proposed that the unfavorable lipid environment and the reduced expression of CFTR may be affecting AQPs functionality. However, whether the alterations of AQPs could play a role in the development of preeclampsia is still unknown.