URIC ACID AND AQP3: NEW INSIGHTS INTO THE PATHOGENESIS OF PREECLAMPSIA

SIERRA, MATIAS N.; FERNANDEZ, NAZARENA; REYNOSO, MARIANO; CASTRO PARODI, MAURICIO; DAMIANO, ALICIA E.

Congreso; Symposium of the Latin American Society on Maternal-Fetal Interaction and Placenta (SLIMP); 2024

Objectives: Preeclampsia is associated with placental insufficiency andincreased syncytiotrophoblast stress. Before the onset of the clinicalsymptoms, serum uric acid levels increase possibly contributing to thedevelopment of the disease. Uric acid is considered a danger-associatedmolecule pattern (DAMP) that could trigger stress and induce the activation of the inflammatory response. Recently, we found that Aquaporin-3(AQP3) is crucial for the migration and endovascular differentiation oftrophoblast cells being downregulated by TNF-alpha. Its expressiondramatically decreased in preeclamptic placentas. High levels of uric acidwere also associated with impaired placentation. We aim to study theconnection between uric acid and AQP3 in trophoblast cells.Methods: BeWo cells were cultured with different concentrations of uricacid (0, 3, 5, and 7 mg/dL). Tunycamicyn 10 mg/ml was used as a control toinduce Endoplasmic Reticulum (ER) stress. Cell viability was analyzed byMTT incorporation. Cell morphology was evaluated by optic microscopy.ER stress markers (XBP1s, CHOP, and BiP) were studied by q-PCR. AQP3expression was assessed by Western blot.Results: Uric acid did not induce ER stress. However, high levels of uric acid(5 and 7 mg/dL) decreased cell viability and the nuclear size (n¼3, P