P10.01: Effects of VEGFR-1 (FLT-1) Inhibition During Pregnancy on the Uterine Circulation of the Mouse

Recent attention has focused on the role of soluble VEGFR-1 (sFlt-1) in the genesis of preeclampsia; less is known about the role of the non-soluble form of this receptor in the maternal uteroplacental circulation during pregnancy. To investigate this question, mice were injected with an anti-VEGFR-1 antibody (35 mg/kg i.p.) every other day beginning on day 8 (n= 9) or 12 (n=11) of gestation; vehicle-only injected mice were used as controls (n=12). All animals were killed late in pregnancy (day 19), prior to onset of parturition for determination of average pup number, resorption rate, and fetal and placental weights. Gestational vascular remodeling was evaluated by measuring the unstressed diameter and length of the main uterine artery and vein, as well as segmental artery diameter and length. Day 8 Ab injection resulted in a reduction in the average number of viable pups from 10 ± 1.2 to 3 ± 1.0 (p<0.01) and a high rate of fetal resorption (75 ± 7% vs. <5% in controls; p<0.05). Reproductive performance was also compromised in the day 12 group, although to a lesser extent. Placental and pup weights were similar throughout. Main and segmental uterine artery diameters were unchanged in either Ab group, although the diameter of the main uterine vein was reduced by 38 and 33% in both 8- and 12-day Ab-injected mice, respectively (p<0.05), Main uterine and segmental artery lengths were also significantly reduced. These results indicate that VEGFR-1 inhibition significantly compromises both reproductive performance and uterine vascular remodeling during murine pregnancy.