Ultrasound-guided selective occlusion of uteroplacental canal vessels in the mouse alters fetal growth and placental development

Placental insufficiency associated with impaired uteroplacental blood flow is the leading cause of human fetal growth restriction. While preclinical studies have examined the effects of global reductions in uterine blood flow, the downstream consequences of a focal disruption in flow remains unknown. We investigate how murine maternal canal occlusion(s) impacts placental development and fetal growth. Pregnant CD-1 mice at embryonic (E) day 15.5 underwent abdominal surgery to exteriorize the uterus. Under ultrasound guidance, zero, one or two of the, typically three, placental canals were microinjected with an embolizing agent. Survival at term (E18.5) was 81% for shams, 62% for single embolized, and 24% for the double embolized. Surviving double embolized fetuses weighed significantly less than both internal and external controls. The brain-to-liver volume ratio was significantly elevated in the singles and doubles versus controls (p = 0.00537, p = 0.00861) and shams (p = 0.01207, p = 0.017738). Placental histopathology, and 3D MRI confirmed, a reduction in junctional zone volume and significantly higher whole placenta-to-junctional zone volume ratio in the single embolized cohort (9.66, 95% CI 8.23-11.1) compared to naïve controls and shams (6.21, 95% CI 4.79-7.63, p = 0.0298; (6.20, 95% CI 4.71-7.70, p = 0.00394, respectively). Canal occlusion resulted in impaired fetal growth and altered placental morphology yet did not cause focal placental infarction typical of impaired uteroplacental blood flow in humans. This placental model of fetal growth restriction may be amenable to testing new intervention strategies aimed at supporting fetal growth when placental function is impaired.