Developmental changes in hemodynamics of uterine artery, utero- and umbilicoplacental, and vitelline circulations in mouse throughout gestation

Abstract

In human pregnancy, abnormal placental hemodynamics likely contribute to the etiology of early-onset preeclampsia and fetal intrauterine growth restriction. The mouse is increasingly being deployed to study normal and abnormal mammalian placental development, yet the placental hemodynamics in normal pregnancy in mice is currently unknown. We used ultrasound biomicroscopy to noninvasively image and record Doppler blood velocity waveforms from the maternal and embryonic placental circulations in mice throughout gestation. In the uterine artery, peak systolic velocity (PSV) increased significantly from 23 ± 2 (SE) to 59 ± 3 cm/s, and end-diastolic velocity (EDV) increased from 7 ± 1 to 28 ± 2 cm/s in nonpregnant versus full-term females so that the uterine arterial resistance index (RI) decreased from 0.70 ± 0.02 to 0.53 ± 0.02. Velocities in the maternal arterial canal in the placenta were low and nearly steady and increased from 0.9 ± 0.03 cm/s at embryonic day 10.5 (E10.5) to 2.4 ± 0.07 cm/s at E18.5. PSV in the umbilical artery increased steadily from 0.8 ± 0.1 cm/s at E8.5 to 15 ± 0.6 cm/s at E18.5, whereas PSV in the vitelline artery increased from 0.6 ± 0.1 cm/s at E8.5 to 4 ± 0.2 cm/s at E13.5 and then remained stable to term. In the umbilical artery, the EDV detection rate was 0% at ≤E14.5 and 94% at E18.5, and the RI decreased from 1 to 0.82 ± 0.01 during this interval. We conclude that ultrasound biomicroscopy can be used to monitor placental hemodynamics during pregnancy in mice. These results provide novel information concerning the development of the vitelline and placental circulations in mice and reveal strong similarities in placental hemodynamics between mice and humans.

Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess

“…Fetal-placental units were imaged over a strict 20-min time period, with a minimum of three units being analyzed in each pregnancy. Blood velocity within the umbilical artery, vein, and placenta was measured (45). Fetal hearts were visualized in B-mode and Doppler measurements were undertaken to determine the E/A wave ratio and myocardial performance index (MPI) (26).…”

Alterations in maternal and fetal heart functions accompany failed spiral arterial remodeling in pregnant mice

“…A thick layer of pre-warmed coupling gel (Ecogel 100; ECO-MED Pharmaceutical, ON, Canada) was applied over the area to be imaged using a 40-MHz transducer probe (Vevo 770, VisualSonics Inc., ON, Canada). 22,26 Body temperature was maintained at 36-37°C by the warmed platform. Maternal heart and respiration rates (ECG/Tm/Resp) were collected using a Physiological Controller Unit.…”

“…22 SA flows, characterized by pulsed waveforms, were imaged at the mesometrial decidual edge in 2-4 implantation sites of each gd10-18 pregnancy. Peak systolic velocities of fetal umbilical arteries (UmA) were recorded before these arteries entered the placenta and branched into chorionic plate arteries (CPA) that run across the placental surface and branch into the major intraplacental arteries (IPA) in developing primary villi.…”

“…After UmA study, peak systolic velocity of CPA and IPA flows were recorded in 3-5 locations/implantation site. 22,23 Maternal left renal artery (RA) flow velocity waveform was recorded to assess systemic blood velocity. For maternal data, 3-6 different females of each genotype were imaged per time-point (i.e.…”

“…Nos3 −/− ) revealed significant similarities to human pregnancies. [20][21][22] Those mouse strains examined by micro-ultrasound have not lacked SA modification, a characteristic of mice deficient in uNK cells. This phenotype is reversible by transplantation of marrow genetically deficient for T and B cell differentiation (ie, NK+, T−B− marrow).…”