Suppression of Trophoblast Uterine Spiral Artery Remodeling by Estrogen During Baboon 4 Pregnancy: Impact on Uterine and Fetal Blood Flow Dynamics

34 35 The present study was conducted to determine the impact of suppressing trophoblast 36 remodeling of the uterine spiral arteries by prematurely elevating estrogen levels in the first 37 trimester of baboon pregnancy on uterine and umbilical blood flow dynamics. Uteroplacental 38 blood flow was assessed by Doppler ultrasonography after acute administration of saline (basal 39 state) and serotonin on days 60, 100 and 160 of gestation (term = 184 days) to baboons in which 40 uterine spiral artery remodeling had been suppressed by the administration of estradiol on days 41 25-59 of gestation. Maternal blood pressure in the basal state was increased (P<0.01) and uterine 42 artery diastolic notching and umbilical artery pulsatility index and systolic/diastolic ratio 43 reflecting downstream flow impedance were increased (P<0.01) after serotonin administration on 44 day 160, but not earlier, to baboons treated with estradiol in early gestation. These changes in 45 uteroplacental flow dynamics in serotonin-infused estradiol-treated animals were accompanied 46 by a decrease (P<0.05) in uterine and umbilical artery volume flow and fetal bradycardia. The 47 results of this study show that suppressing uterine artery remodeling by advancing the rise in 48 estrogen from the second to the first trimester disrupted uteroplacental blood flow dynamics and 49 fetal homeostasis after vasochallenge late in primate pregnancy. 50 51