Advertisement

41: Synergistic effect of prepregnancy obesity and sFlt1-induced preeclampsia on fetal programming of adult vascular function

      Objective

      To test the hypothesis that prepregnancy obesity and sFlt1-induced preeclampsia lead to altered vascular function in the offspring later in life.

      Study Design

      CD-1 female mice were placed on low (LF; 4.3 gm% fat) or high fat (HF; 34.9 gm% fat) diet for 12-14 weeks before mating. On day 8 of pregnancy, mice in the HF group were injected with adenovirus carrying sFlt1 (HFsFlt1 group) or adenovirus carrying mFc as virus control (HFmFc group). After weaning, all offspring were placed on a standard diet containing 5.6% fat. At 12 weeks of age, the right carotid artery was isolated for in-vitro vascular reactivity studies (n=10-12 per group). Concentration-response curves to phenylephrine, thromboxane, serotonin, acetylcholine, sodium nitroprusside and isoproterenol were obtained. ANOVA with Bonferroni post hoc test were used for analysis (significance: p<0.05).

      Results

      At the time of breeding, HF mice were significantly heavier than LF. There were no differences in pup weight, weight at 12 weeks, weight of visceral fat, or visceral fat/body weight ratio between the groups when comparing within the same gender. Males in all groups were significantly heavier than females, with no difference in fat tissue weight. In HFsFlt1 group, fasting glucose was significantly higher in males compared with females. Responses to serotonin in males and to thromboxane in females were significantly lower in both HF groups compared to the LF group. Among males, responses to phenylephrine were significantly lower in HFsFlt1 compared to HFmFc or LF. Within the HFsFlt1 and LF groups, responses to phenylephrine were significantly lower in females compared to males. Responses to thromboxane were lower in females versus males in both HF groups, but not in the LF group.

      Conclusion

      Prepregnancy obesity alters fetal programming of adult vascular function, and this effect is amplified by preeclampsia, particularly in female offspring. The mechanism is complex and gender-specific. Prevention of prepregnancy obesity or preeclampsia can have significant impact on long term health in the offspring.