EVIDENCE FOR OXYGEN-MEDIATED CONTROL OF CFTR AND CAVEOLIN-1 IN HUMAN PLACENTAS

SZPILBARG N; SEHAYIAN A; MEDINA Y; DI PAOLA M; MARTÍNEZ N.; FARINA M; DAMIANO A

Buenos Aires

Congreso; REUNION CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

It has been proposed that intermittent placental perfusion, secondary to deficient trophoblast invasion of the endometrial arteries, leads to an ischemia-reperfusion type insult in preeclamptic placentas (PE). Such variations in oxygenation can further alter the syncytiotrophoblast functions. We have previously reported that the cystic fibrosis transmembrane conductance regulator (CFTR) is significantly reduced in PE. In addition, we have recently reported alterations in the membrane lipid composition of the apical membrane of syncytiotrophoblast (hST) of PE. Therefore, we also detected that the expression Caveolin-1, the major structural component of caveolas, was reduced in these membranes. Our aim was to identify the mechanisms implicated in the regulation of CFTR and Caveolin-1(Cav-1) expression. We hypothesized that intermittent hypoxia may be responsible for the altered expression of both proteins.Localization of CFTR and Cav-1 expressions were studied by double immunofluorescence in normal placentas and PE (n=13). To study the role of oxygen, explants from normal placenta were cultured in normoxia, hypoxia, and hypoxia/reoxygenation (H/R) and the mRNA and protein expressions of CFTR and Caveolin-1 were determined. In normal placentas, both proteins co-localized in the apical membrane of the hST, but the colocalization was lost in PE. CFTR expression decreased 2-fold (n=6; p