Cloprostenol, a prostaglandin F_2α analog, induces hypoxia in rat placenta: BOLD contrast MRI

Abstract

Blood oxygen level dependent (BOLD) contrast was used to monitor hypoxia induced by cloprostenol, a prostaglandin F(2alpha) (PGF(2alpha)) analog, in the rat embryo-placental unit (EPU). It is shown that administration of cloprostenol (0.025 mg/rat) at mid-gestation (day 16) reduced EPU oxygenation, as detected by BOLD contrast MRI, in correlation with induction of vascular endothelial growth factor (VEGF) gene (Vegfa) expression in the corresponding placenta (r = 0.56, p = 0.03). Elevated VEGF mRNA expression in response to cloprostenol treatment was also observed at early gestation (day 9) in the forming placenta (p = 0.04) and uterus (p = 0.03). Cloprostenol increased the expression levels of endothelin-1 (ET-1) gene (Edn1) (p = 0.03) and its corresponding peptide (p = 0.02) in the forming placenta, as well as the expression of the endothelin receptor type A (ETA) gene (Ednra) in both the forming placenta (p = 0.009) and the uterus (p = 0.01). The levels of the endothelin receptor type B (ETB) gene (Ednrb) were not affected in response to cloprostenol, but a significant elevation in the expression level of this receptor was observed in the uterus at mid- and late gestation (day 22) (p = 0.04 and 0.01 respectively), suggesting a role for ETB in the vasodilatory status of the pregnant uterus. It is suggested that PGF(2alpha) induces uteroplacental vasoconstriction in the rat, and that ET-1 may take part in mediating this effect, probably via activation of ETA receptor. The uteroplacental vasoconstriction induces hypoxia, as manifested by significant changes in BOLD MRI and by upregulation of VEGF.

Placental magnetic resonance imaging T2* measurements in normal pregnancies and in those complicated by fetal growth restriction

“…To our knowledge, this is the first study on placental T2* in human FGR pregnancies. However, two animal studies have been published demonstrating a reduced placental T2* value during experimental FGR and hypoxia. Human placental T2 measurements have been described in a few FGR studies.…”

Functional imaging of the human placenta with magnetic resonance

“…80 OE-MRI is a technique that is very similar to BOLD-MRI, which measures decreases in T1 under oxygen challenge, usually assumed to be due to increases in the partial pressure of dissolved oxygen. 81 Animal studies There are several animal studies on OEand BOLD-MRI in pregnancy, 24,25,30,[82][83][84][85][86] and these techniques may allow detection of abnormal oxygenation or perfusion. Maternal hypoxia in sheep leads …”

Magnetic Resonance Imaging Detects Placental Hypoxia and Acidosis in Mouse Models of Perturbed Pregnancies

“…Magnetic Resonance Imaging (MRI) studies of placental anatomy and perfusion have been conducted in humans [4]–[6], mice [7]–[9] and rats [10]. While dynamic contrast-enhanced MRI, using injected contrast agents, has yielded estimates of mean blood flow in the placenta of animals [11] non-invasive techniques such as arterial spin labelling, diffusion imaging and measurements of T 1 (spin-lattice or longitudinal) and T 2 (spin-spin or transverse) relaxation times have been investigated to provide alternative safe techniques for assessing human placental structure and function [12].…”