UT-A expression in normal and preeclamptic placentas

DAMIANO ALICIA E; ZOTTA ELSA; IBARRA CRISTINA

Cambridge

Simposio; International Symposium on Membrane Transport and Transporters; 2004

Biochemical Society UK

Normal fetal growth and development is critically dependent on sufficient transport of nutrients, metabolites, ions and water across the placenta. The syncytiotrophoblast of term human placenta (hST) is a continuous multinucleated structure with minimal tight junctions, which results from the fusion of the underlying cytotrophoblast cells. Thus, the transport of metabolites, ions and water from mother to fetus could take place primarily via transcellular routes. Transcellular water and urea transport across hST may be facilitated by aquaporins (AQPs), water permeable membrane proteins widely expressed in cells and tissues and/or by urea tranporters type UT. We previously reported the expression and localization of three aquaglyceroporins: AQP3, AQP7 and AQP9 in hST. AQP9 allows the rapid passage of water, urea, glycerol and a wide variety of non-charged solutes. We have observed by Western blot and immunohistochemical analyses that AQP9 expression is increased in preeclamptic pregnancies. Despite of this, in preeclamptic placentas water and mannitol unnidirectional fluxes, are not increased and they are not inhibit by HgCl2. Recently, we have determined the expression and localization of an urea transporter type A (UT-A) in normal and preeclamptic term placenta, by RT-PCR, immunoblotting, and immunocytochemistry. We observed a molecular expression decreased of UT-A in preeclamptic placentas. In order to evaluate their functionality, explants from normal and preeclamptic placentas were cultured in DMEM for 24 h. Undirectional fluxes of 14C-urea were measured. In both cases, the incorporation of 14C-urea was inhibited by phloretin 0.5 mM and by HgCl2 0.3 mM. In preeclamptic explants, however, urea uptake was significantly higher than in normal tissues. These results demonstrate that functional UT-A is present in placental villuous and its functionality increased in preeclamptic placentas. Further experiments will be needed to elucidate the importance of UT-A in the transport between mother to fetus and in the etiology of preeclampsia.