Vascular Endothelial Growth Factor Delivery to Placental Basal Plate Promotes Uterine Artery Remodeling in the Primate

作者: Jeffery S Babischkin , Graham W Aberdeen , Jonathan R Lindner , Thomas W Bonagura , Gerald J Pepe

DOI: 10.1210/EN.2019-00059

关键词: Internal medicineVascular endothelial growth factorBasal plate (neural tube)FetusUterine arteryIn vivoBaboonTransfectionGene deliveryMedicineEndocrinology

摘要: Extravillous trophoblast (EVT) uterine artery remodeling (UAR) promotes placental blood flow, but UAR regulation is unproven. Elevating estradiol (E2) in early baboon pregnancy suppressed and EVT vascular endothelial growth factor (VEGF) expression, this did not prove that VEGF mediated process. Therefore, our primate model of prematurely elevating E2 contrast-enhanced ultrasound cavitation microbubble (MB) carriers was used to deliver DNA the basal plate (PBP) establish role UAR. Baboons were treated on days 25 59 gestation (term, 184 days) with alone or plus DNA-conjugated MBs briefly infused via a maternal peripheral vein 25, 35, 45, 55. At each these times an beam directed PBP collapse release DNA. DNA-labeled per contrast agent localized fetus. Remodeling arteries >25 µm diameter day 60 75% lower (P < 0.001) E2-treated (7% ± 2%) than untreated baboons (30% 4%) restored normal by E2/VEGF. protein levels (signals/nuclear area) within twofold 0.01) (4.2 0.9) (9.8 2.8) E2/VEGF (11.9 1.6), substantiating transfection. Thus, gene delivery selectively prevented decrease elicited levels, establishing regulating vivo during pregnancy.

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