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LTP Nanoparticles Seeded with Plasmid for Vascular Endothelial Growth Factor Receptor 2 Improve Fetal Morphometrics in a Rat Model of Preeclampsia

Recent studies by our lab have demonstrated that the delivery of L‐Tyrosine Phosphate nanoparticles seeded with plasmid for Vascular Endothelial Growth Factor Receptor 2 (LTP VEGFR2) normalizes mean arterial pressure, uterine vessel myogenic reactivity, and fetal growth restriction in the reduced uterine perfusion pressure (RUPP) animal model. The goal of this study was to investigate fetal morphometrics in RUPP+LTP VEGFR2 dams. For the RUPP procedure, silver clips are placed on the abdominal aorta (0.2mm i.d.) below the kidneys and the utero‐ovarian arteries (0.1mm i.d.) on day 14 of pregnancy in Sprague‐Dawley rats. SHAM pregnant rats undergo the same surgery without the clip placement. On the same day as surgery, LTP nanoparticles encapsulated with plasmid DNA encoding for VEGF Receptor 2 (VEGFR2), or nonsense were injected into the uterine wall. On day 21 of gestation, the uterus was removed and fetal weights, placental weights, and head circumference were recorded on three fetuses from each dam. The fetuses were selected based on position in the uterus in relation to the site of injection of the LTP nanoparticles. Fetal position was designated as the following: Site 1 was selected as the closest to the injection site, Site 6 was distal in the same uterine horn, and Site 14 was contralateral to Site 6. Fetal weight for pups at Site 1 was significantly increased in RUPP rats treated with VEGFR2 nanoparticles compared to RUPP treated with nonsense nanoparticles (4.70g ± 0.44 vs. 3.89g ± 0.31; p<0.05). Placental weight at Site 1 was significantly increased in RUPP rats treated with VEGFR2 nanoparticles compared to RUPP treated with nonsense nanoparticles (0.635g ± 0.06 vs. 0.491g ± 0.04; p<0.05). Head circumference was also significantly increased in pups at site 1 in RUPP rats treated with VEGFR2 nanoparticles as compared RUPP rats treated with nonsense nanoparticles (2.37cm ± 0.32 vs. 1.45cm ± 0.07; p<0.05). There were no significant differences in fetal weights, placental weights and head circumference in the SHAM group at any of the fetal positions. Furthermore, there were no significant differences when comparing between the SHAM and RUPP groups. The fetal measurements (fetal weight, placental weight and fetal head circumference) from RUPP treated with nonsense nanoparticles tended to be lower compared to the other groups (SHAM treated with VEGFR2 nanoparticles, SHAM treated with nonsense nanoparticles or RUPP treated with VEGFR2 nanoparticles; however, it failed to reach significance in this preliminary study. In conclusion, uterine injection of LTP nanoparticles with plasmid DNA encoding for VEGFR2 improved fetal morphometrics in RUPP animals.