265: Fetal programming of adult blood pressure in a mouse model of pre-pregnancy obesity and preeclampsia


      To test the hypothesis that pre-existing maternal obesity and preeclampsia lead to altered blood pressure in the offspring later in life, using well-established mouce models of obesity and preeclampsia-like syndrome induced by sFlt-1 overexpression.

      Study Design

      CD-1 female mice were place on either low fat (LF; 4.3 gm% fat) or high fat (HF; 34.9 gm% fat) diet for 12-14 weeks before mating. On day eight of pregnancy, mice in the HF group were injected with adenovirus carrying sFlt1 (HFsFlt1) or adenovirus carrying mFc as virus control (HFmFc). After weaning, offspring from the 3 groups were placed on a standard diet containing 5.6% fat (n=10-12 per group). At 12 weeks of age, blood pressure (BP) was measured continuously in conscious unrestrained male offspring using implanted telemetric transducers. One-way and repeated measure ANOVA with Bonferroni post hoc test were used for analysis (significance p<0.05).


      There were no differences in weight at birth, body weight at 12 weeks of age, weight of visceral fat, or visceral fat/body weight ratio between the offspring groups. Locomotor activity was significantly lower in offspring from HFsFlt1 group compared with LF (p<0.04). Mean and systolic BP were significantly higher in offspring born to HFsFlt1 group mothers compared with the other groups (p<0.001). There were no differences in diastolic BP, heart rate, or pulse pressure between the 3 groups.
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      Pre-pregnancy maternal obesity with superimposed sFlt1-induced preeclampsia, but not obesity alone, leads to hypertension and lower motor activity in the offspring later in life. Prevention of pre-pregnancy obesity and/or preeclampsia can have significant impact on long term health in the offspring.