Evidence for oxygen-mediated regulation of aqp4 expression in human placenta

N. SZPILBARG; J. REPPETTI; M. DI PAOLA; M. CASTRO-PARODI; N. MARTÍNEZ,; M. FARINA; A.E. DAMIANO

Simposio; Latin American Society for Maternal Fetal Interaction and Placenta; 2017

Preeclampsia is a multisystem syndrome unique to human pregnancy.Aberrations in the remodelling of the spiral arteries lead to fluctuations inthe oxygen tension within the placenta. The resulting over-expression ofhypoxia inducible factor 1a (HIF-1a) contributes to the dysregulation ofnumerous genes, which perturbs normal placental functions. Theexpression of a variety of syncytiotrophoblast transporters is abnormal inplacentas from women with preeclampsia.Objective: To study the expression of Aquaporin-4 (AQP4) in placentasfrom women with preeclampsia and the effects of changes in oxygentension on AQP4 expression in placental villous tissue.Methods: Placental tissue from full-term normal pregnancy and preeclampsiawere obtained. Normal placental tissue was cultured underdifferent oxygen conditions (20 or 2% O2). Some explants were treatedwith 250 mM CoCl2 (a hypoxia mimicking agent that inhibits HIF-1a).Tissue viability was assessed by the MTT. AQP4 protein expression wasanalysed by Western blot and immunohistochemistry. A theoreticalanalysis of the promoter region of the AQP4 genewas carried out using theMatInspector tool from Genomatix.Results: In placentas from preeclampsia AQP4 was weakly detectable. Inexplants from normal placenta cultured in hypoxia (2% O2) AQP4 proteinexpression increased (1.7 ± 0.3 fold) (P