Intravital high-frequency ultrasonography to evaluate cardiovascular and uteroplacental blood flow in mouse pregnancy

Objective: The objective of this study is to define the ultrasonographic changes in the cardiovascular and uteroplacental circulation of normal pregnant mice compared to non-pregnant mice using high-frequency, high-resolution ultrasonography. Methods: Ten to twelve-week-old CD-1 mice (six non-pregnant and six pregnant animals) were used for all experiments. Vevo (R) 2100 (VisualSonics) was used to evaluate the cardiovascular and uteroplacental circulation physiology. Cardiac echocardiogram and uterine artery Doppler studies were performed on all animals. Pregnant animals were evaluated on embryonic day 7 (E7), 13 (E13) and 18 (E18). Fetal heart rate and umbilical artery Doppler flows were obtained on pregnant animals. Three-dimensional ultrasonography imaging was utilized for quantification of placental volumes. All data are presented as median (10th-90th percentiles). Results: In pregnant mice on E7 compared to non-pregnant mice, there was an increase in cardiac output (p = 0.008), stroke volume (p = 0.002), ejection fraction (p = 0.02), and fractional shortening (p = 0.02). The maternal heart rate increased throughout gestation (p = 0.009). During pregnancy, a gestational sac was clearly visible on E7. Between E13 and E18, the fetal size and fetal heart rate increased (p = 0.001) and the umbilical artery peak systolic velocity increased (p < 0.001). Minimal diastolic blood flow was observed in the umbilical artery on E13, which increased slightly on day E18 (p = 0.01). There was no change in the uterine artery resistance index between non-pregnant and pregnant mice. The placental volume increased between E13 and E18 (p = 0.03). Conclusion: Several changes noted in cardiovascular and uteroplacental systems occurring during normal murine pregnancy have striking similarities to humans and can be accurately measured using newer ultrasonographic techniques. Further studies are needed to evaluate changes in these vascular beds in mouse models of diseases such as preeclampsia and intrauterine growth restriction. (C) 2011 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.