HIGH LEVELS OF TUMOR NECROSIS FACTOR-ALPHA REDUCES PLACENTAL AQUAPORIN 3 EXPRESSION AND IMPAIRS IN VITRO TROPHOBLASTIC CELL MIGRATION

RODRIGUES DOS PASSOS JUNIOR, RINALDO; ALVES DE FREITAS, RAIANY; REPPETTI, JULIETA; MEDINA, YOLLYSETH; DELA JUSTINA, VANESSA; WERLE BACH, CAMILA; FACHOLI BOMFIM, GISELE; VITORINO LIMA, VICTOR; DAMIANO, ALICIA E; GIACHINI, FERNANDA

Amsterdam (Virtual)

Congreso; International Federation of Placenta Associations (IFPA) meeting 2021; 2021

Objectives: To characterize if elevated levels of TNF-a, observed duringhypertensive pregnancy, reduces the AQP3 expression and abrogatestrophoblast cells migration.Methods: Pregnant spontaneously hypertensive rats (SHR, n¼6) andnormotensive Wistar rats (n¼6) were used. In a third group, pregnantSHRs (n¼8) were treated with a TNF-a antagonist, etanercept (0.8 mg/kg,i.p.) on days 0, 6, 12, and 18 of pregnancy. Systolic blood pressure (SBP) wasmeasured by tail-cuff plethysmography.On the 21st day of pregnancy,placentas were collected. Human placental explants, from normotensivepregnancies, were incubated with TNF-a (5, 10 and 20 ng/mL) and/oretanercept (1 mg/mL). Swan 71 cells were incubated with TNF-a (10 ng/mL)and/or etanercept (1 mg/mL) and subjected to the wound healing assay.AQP3 expression was assessed by western blot and TNF-a levels by ELISA.Results: SBP (mmHg) was elevated in the hypertensive group (181±3 vs.128±5 normotensive), and etanercept treatment reduced this parameter(163±2). Placental TNF-a levels (pg/mL) were higher in the hypertensivegroup (3±0.1 vs. 1.5±0.3 normotensive; p¼0.003). AQP3 expression wasreduced in the hypertensive group, and etanercept treatment reversed thisparameter. Explants submitted to TNF-a exposition displayed reducedexpression of AQP3 and etanercept incubation reversed it. Trophoblasticcells incubated with TNF-a showed decreased cell migration and reducedAQP3 expression and etanercept incubation ameliorated it.Conclusion: Altogether, these data demonstrate that high TNF-a levelsnegatively modulates AQP3 in placental tissue, impairing c