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

Eliezer Girsh, Vicki Plaks, Assaf A. Gilad, Nava Nevo, Edna Schechtman, Michal Neeman, Nava Dekel

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Blood oxygen level dependent (BOLD) contrast was used to monitor hypoxia induced by cloprostenol, a prostaglandin F. (PGF) analog, in the rat embryo-placental unit (EPU). It is shown that administration of cloprosteno (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 = 0.0 1). 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 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.

Original languageEnglish
Pages (from-to)28-39
Number of pages12
JournalNMR in Biomedicine
Volume20
Issue number1
DOIs
StatePublished - 1 Feb 2007

Keywords

  • BOLD MRI
  • Cloprostenol
  • Endothelin
  • Hypoxia
  • PGF analog
  • Placenta
  • Uterus
  • VEGF

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Spectroscopy

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