Suppression of trophoblast uterine spiral artery remodeling by estrogen during baboon pregnancy: impact on uterine and fetal blood flow dynamics

Abstract

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

High Maternal Serum Estradiol Environment in the First Trimester Is Associated With the Increased Risk of Small-for-Gestational-Age Birth

“…Animal experiments showed that an elevated serum E 2 level in the first trimester of pregnancy would suppress extravillous cytotrophoblast spiral artery invasion, impair blood flow to the placenta, and lead to fetal growth restriction (17). One of the complications of suppressed uterine artery invasion could be poor placental perfusion (26). In the present study, no significant difference was found between the high-E 2 and low-E 2 groups in placenta growth.…”

Why we should transfer frozen instead of fresh embryos: the translational rationale

“…In multiple studies of nonhuman primates, Albrecht et al have shown that exogenous estrogen given during early pregnancy impairs extravillous trophoblast invasion of the uterine spiral arteries (75, 76). That group has also found that premature elevation of estrogen in early pregnancy reduces uterine vessel remodeling and leads to abnormal uteroplacental blood flow dynamics (77). …”

Evaluation of Uterine Artery Doppler and Estrogen Milieu in Oocyte Donation Pregnancies—A Pilot Study

“…In pregnant women, no differences were found in the mean RI of uterine and spiral arteries between intrauterine and ectopic human pregnancies, suggesting that uterine vascular changes occur even if placentation occurs outside the uterine cavity [20]. In baboon pregnancy, it was demonstrated that prematurely elevating estrogen levels in the first trimester can suppress trophoblastic remodeling of the uterine spiral arteries [21]. This evidence needs to be considered in OD cycles.…”