Uterine spiral artery remodeling (UAR) is essential for placental perfusion and fetal development. A defect in UAR underpins placental ischemia disorders, e.g. preeclampsia, that result in maternal systemic vascular endothelial oxidative stress and dysfunction and hypertension. We have established a model of impaired UAR by prematurely elevating maternal serum estradiol levels during the first trimester of baboon pregnancy. However, it is unknown whether this experimental paradigm is associated with maternal vascular endothelial dysfunction. Therefore, in the present study baboons were administered estradiol on days 25-59 of gestation to suppress UAR and vascular function determined in maternal skeletal muscle obtained on day 165 (term = 184 days). Maternal peripheral serum sFlt-1 levels were 3-fold higher (P <0.05) and skeletal muscle arteriolar endothelial nitric oxide synthase protein expression and luminal area, and skeletal muscle capillary density, were 30-50% lower (P < 0.01) near term in UAR suppressed baboons. Maternal skeletal muscle catalase protein levels, reflecting oxidative stress, were 75% higher (P < 0.05) and mean arterial blood pressure 28% higher (P < 0.01) in UAR defective baboons. We propose that these changes in skeletal muscle, a systemic tissue, were induced by the elevation in sFlt-1, which suppresses vascular endothelial growth factor bioavailability. In summary, maternal skeletal muscle vascular function was disrupted in a baboon model of impaired UAR. These results highlight the translational impact of this primate model and relevance to adverse conditions of human pregnancy underpinned by improper uterine artery transformation.
Inhibition of Trophoblast-Induced Spiral Artery Remodeling Reduces Placental Perfusion in Rat Pregnancy
