title: Intravital high-frequency ultrasonography to evaluate cardiovascular and uteroplacental blood flow in mouse pregnancy.
abstract: 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® 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 seven (E7), thirteen (E13) and eighteen (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 {10(th)-90(th) 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 also 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.
authors.affiliation: Department of Medicine/Division of Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Eliyahu V
authors.initials: EV
authors.lastname: Khankin
authors.forename: Michele R
authors.initials: MR
authors.lastname: Hacker
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Zelop
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.forename: Sarosh
authors.initials: S
authors.lastname: Rana