Abstract
The discrete regulation of vascular tone in the human uterine and placental circulations is a key determinant of appropriate uteroplacental blood perfusion and pregnancy success. Humoral factors such as estrogen, which increases in the placenta and maternal circulation throughout human pregnancy, may regulate these vascular beds as studies of animal arteries have shown that 17β-estradiol, or agonists of estrogen receptors (ER), can exert acute vasodilatory actions. The aim of this study was to compare how acute exposure to ER-specific agonists, and 17β-estradiol, altered human placental and uterine arterial tone in vitro. Uterine and placental arteries were isolated from biopsies obtained from women with uncomplicated pregnancy delivering a singleton infant at term. Vessels were mounted on a wire myograph, exposed to the thromboxane receptor agonist U46619 (10−6 M), and then incubated with incremental doses (5 min, 0.03–30 µM) of either 17β-estradiol or agonists specific for the ERs ERα (PPT), ERβ (DPN) or the G-protein-coupled estrogen receptor GPER-1 (G1). ERα and ERβ mRNA expression was assessed. 17β-estradiol, PPT and DPN each relaxed myometrial arteries (P < 0.05) in a manner that was partly endothelium-dependent. In contrast, 17β-estradiol or DPN relaxed placental arteries (maximum relaxation to 42 ± 1.1 or 47.6 ± 6.53% of preconstriction, respectively) to a lesser extent than myometrial arteries (to 0.03 ± 0.03 or 8.0 ± 1.0%) and in an endothelial-independent manner whereas PPT was without effect. G1 exposure did not inhibit the constriction of myometrial nor placenta arteries. mRNA expression of ERα and ERβ was greater in myometrial arteries than placental arteries. ER-specific agonists, and 17β-estradiol, differentially modulate the tone of uterine versus placental arteries highlighting that estrogen may regulate human uteroplacental blood flow in a tissue-specific manner.
Highlights
A key determinant of appropriate fetal growth during human pregnancy is the transfer across the placental epithelium of oxygen and nutrients between the uterine and fetal circulations
This study is the first to investigate the potential role of estrogen and estrogen receptors in acutely regulating the vasoreactivity of arteries isolated from these circulations at the end of pregnancy
Our results demonstrate that the relaxatory influences of 17b-estradiol or estrogen receptors (ER)-specific agonists differ between myometrial and placental arteries
Summary
A key determinant of appropriate fetal growth during human pregnancy is the transfer across the placental epithelium of oxygen and nutrients between the uterine and fetal circulations. As the two circulations are separate physical entities—blood from the maternal uterine circulation that traverses through the lumen of terminal open-ended spiral arterioles is directed towards the syncytial surface of the placenta but does not come in to direct contact with the enclosed fetoplacental circulatory flow— materno-fetal nutrient exchange will be influenced by changes in either the uterine or placental vasculatures. This makes it important to understand how the blood vessels from each circulation respond to physiological vasoactive factors. These may be mediated via endothelial-dependent and/or -independent mechanisms
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