Figure 5. Sildenafil treatment in sFlt1-expressing dams improves fetal outcomes by enhancing uterine blood flow.

(A) Live birth weights from mice injected at gd8 with sFlt1 adenovirus and randomized to sildenafil (sFlt1 + SILD, n = 7 dams) or water (sFlt1, n = 8 dams) at gd12. Plasma sFLT1 was similar prior to randomization. *P < 0.001. (B) Live birth weights showing distribution by birth date (gd). Pups born to sFlt1 + SILD dams (n = 7) had higher birth weights compared with those born to sFlt1 dams (n = 8), independent of date of birth. *P < 0.001. Data presented as boxplot (median, interquartile ranges, minimum and maximum), analyzed by 1-way ANOVA with Tukey’s post-hoc test. (C) Placental histology from gd17 mice given sFlt1 or sFlt1 + SILD. Scale bar: 50 μm. (D and E) Representative Doppler waveform of the uterine artery at gd16 in sFlt1-treated (D) and sFlt1 + sildenafil–treated mice (sFlt1 + SILD) (E), highlighting differences in total flow (peak amplitude) and resistance (height of end diastolic velocity). (F) Uterine artery peak systolic velocity (PSV) and end diastolic velocity (EDV) obtained at gd16 via Doppler ultrasound (n = 5 per group). Sildenafil treatment increases EDV in comparison with sFlt1-only mice. *P < 0.05. (G) Uterine artery resistance index was reduced in the sFlt1 + SILD group compared with sFlt1 alone (n = 5 per group). Data are mean ± SEM, analyzed by unpaired 2-tailed t test, except where noted. *P < 0.05.