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Human uterine and placental arteries exhibit tissue-specific acute responses to 17β-estradiol and oestrogen-receptor-specific agonists

Lookup NU author(s): Professor Steve Robson, Professor Michael Taggart

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.


Publication metadata

Author(s): Corcoran JJ, Nicholson C, Sweeney M, Charnock JC, Robson SC, Westwood M, Taggart MJ

Publication type: Article

Publication status: Published

Journal: Molecular Human Reproduction

Year: 2014

Volume: 20

Issue: 5

Pages: 433-441

Print publication date: 01/05/2014

Online publication date: 01/05/2014

Acceptance date: 04/12/2013

Date deposited: 05/08/2015

ISSN (print): 1460-2407

ISSN (electronic): 1360-9947

Publisher: Oxford Journals

URL: http://dx.doi.org/10.1093/molehr/gat095

DOI: 10.1093/molehr/gat095

PubMed id: 24356876

Notes: epub:19/12/2013


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