202. Joint exposure to antiangiogenesis and inflammation in pregnant mice results in sex specific growth restriction patterns

Introduction Preeclampsia is a multifactorial pregnancy disorder presented with angiogenic imbalance and low-grade systemic inflammation. However, animal models which represent these variety of pathophysiological conditions are missing. Objective/hypothesis We aimed to establish a novel double hit preeclampsia animal model in order to mimic the complex multifactorial conditions that are present during preeclampsia and to investigate the early consequences to the fetus. Methods C57Bl/6 mice on gestational day GD 8.5 were injected with adenovirus overexpressing sFlt-1 (1 × 10 9 PFU in 100 ml) or empty adenovirus. On GD 10, a second hit was introduced with a low dose of lipopolysaccharide (LPS, 25 μg/kg, i.p.) or PBS. Between GD 16.5 and 17.5, 24-h urine was collected. Blood pressure and blood analysis were performed on GD 18.5. Fetuses and placentas were collected at GD 18.5. Results Animals exposed to sFlt-1 and LPS showed increased blood pressure and albumins in 24-h urine. sFlt-1 concentrations were 2×higher in the double hit preeclampsia group. Blood pressure values were positively correlated with the sFlt-1 concentrations. Fetuses were growth restricted and subclassification based on sex showed that females have symmetrical growth restriction accompanied with smaller placentas in comparison to male fetuses. In continuation male fetuses showed asymmetrical growth restriction, accompanied by brain sparring. Discussion Our results show that combined exposure to sFlt-1 and LPS mimics the symptoms of preeclampsia in a mouse model and affects fetal growth in a sex-specific manner.