EVIDENCE FOR OXYGEN-MEDIATED REGULATION OF AQP4 EXPRESSION IN HUMAN PLACENTA

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

Puerto Varas

Simposio; SLIMP- Latin American Society for Maternal Fetal Interaction and Placenta and SCHCF- Sociedad Chilena de Ciencias Fisiológicas; 2017

SLIMP

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<0.05, n ¼ 8) but it was significantlydecreased (48 ± 7%) (P<0.01, n ¼ 8) following reoxygenation. The in-silicoanalysis showed three putative binding sites for HIF-1a in AQP4 promoter.Incubation of explants with CoCl2 increased AQP4 protein level (1.8 ± 0.16fold) (P<0.01, n ¼ 8).Conclusions: These data suggest that AQP4 expression is abnormal inplacentas from womenwith preeclampsia, possibly because of fluctuationsin oxygen tension within the placenta. We propose that oxygen mayregulate the expression of placental AQP4 probably through a HIF-1adependent pathway.