SMFM meeting paper
Gender-specific effect of overexpression of sFlt-1 in pregnant mice on fetal programming of blood pressure in the offspring later in life

Presented at the 27th Annual Clinical Meeting of the Society for Maternal-Fetal Medicine, San Francisco, CA, Feb. 5-10, 2007.
https://doi.org/10.1016/j.ajog.2007.06.064Get rights and content

Objective

The purpose of this study was to determine whether fetal programming of adult blood pressure is altered in a previously characterized mouse model of preeclampsia that was induced by sFlt-1.

Study Design

CD-1 mouse mothers at day 8 of gestation were injected with an adenovirus carrying Flt 1-3 (109 plaque-forming units) or with an adenovirus carrying mFc as control (109 plaque-forming units). The resulting pups were followed until 6 months of age, at which time blood pressure (BP) was recorded continuously for 6 days. The offspring weight was also recorded from weaning until adulthood.

Results

BP was significantly higher in the male offspring that were born to sFlt-1–treated mothers compared with the controls. Male offspring from sFlt-1–treated mothers were significantly smaller from weaning until adulthood. However, there were no significant differences in BP and postweaning weight in female offspring between the 2 groups.

Conclusion

Our findings highlight the role of the intrauterine environment in the developmental origin of adult disease.

Section snippets

Animals

Pregnant CD-1 mice at day 6 of gestation were purchased from Charles River (Wilmington, MA). The mice were housed separately in temperature- and humidity-controlled quarters with constant 12-hour light:dark cycles and provided with food and water ad libitum. At day 8 of gestation, pregnant CD-1 mice were divided randomly into 2 groups and injected through the tail vein with either adenovirus carrying sFlt-1 (109 plaque-forming units in 100 μL; sFlt-1 group) or adenovirus carrying the murine

Weight after weaning

The male and female offspring from sFlt-1– and mFc-treated pregnant mice were followed until adulthood. The weight from weaning until adulthood of male offspring that were born to sFlt-1–treated pregnant mice was significantly lower than male offspring that were born to mFc-treated pregnant mice (Figure 1A). There was no significant difference in the postweaning weight in female offspring between the 2 groups (Figure 1B).

BP results in male offspring

Mean BP was significantly higher during the entire measurement period in

Comment

We found that systolic, diastolic, and mean BPs of male offspring at 6 months of age that were born to pregnant mothers that were injected with adenovirus carrying sFlt-1 were significantly higher than the similarly aged male offspring from mFc-treated pregnant mothers (adenovirus carrying the murine immunoglobulin G2α Fc fragment as a control) and that these differences were not present in female offspring at the same age that were born to sFlt-1– and mFc-treated mothers. There were no

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    Cite this article as: Lu F, Bytautiene E, Tamayo E, et al. Gender-specific effect of overexpression of sFlt-1 in pregnant mice on fetal programming of blood pressure in the offspring later in life. Am J Obstet Gynecol 2007;197:418.e1-418.e5.

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