Review: Water channel proteins in the human placenta and fetal membranes.

It has been established that the permeability of the human placenta increases with advancing gestation. Indirect evidence has also proposed that aquaporins (AQPs) may be involved in the regulation of placental water flow but the mechanisms are poorly understood. Five AQPs have been found in the human placenta and fetal membranes [AQP1, 3, 4, 8 and 9]. However, the physiological function(s) and the regulation of these proteins remain unknown. Emerging evidence has shown that human fetal membrane AQPs may have a role in intramembranous amniotic fluid water regulation and that alterations in their expression are related to polyhydramnios and oligohydramnios. In addition, we have observed a high expression of AQP3 and AQP9 in the apical membrane of the syncytiotrophoblast. Moreover, AQP9 was found to be increased in preeclamptic placentas, but it could not be related to its functionality for the transport of water and mannitol. However, a significant urea flux was seen. Since preeclampsia is not known to be associated with an altered water flux to the fetus we propose that AQP9 might not have a key role in water transport in human placenta, but a function in the energy metabolism or the urea uptake and elimination across the placenta. However, the role of AQP9 in human placenta is still speculative and needs further studies. Insulin, hCG, cAMP and CFTR have been found to be involved in the regulation of the molecular and functional expression of AQPs. Further insights into these mechanisms may clarify how water moves between the mother and the fetus.