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Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia.

Abstract
Fetal growth restriction (FGR) and preeclampsia (PE) are often associated with abnormal maternal inflammation, deficient spiral artery (SA) remodeling, and altered uteroplacental perfusion. Here, we provide evidence of a novel mechanistic link between abnormal maternal inflammation and the development of FGR with features of PE. Using a model in which pregnant rats are administered low-dose lipopolysaccharide (LPS) on gestational days 13.5-16.5, we show that abnormal inflammation resulted in FGR mediated by tumor necrosis factor-α (TNF). Inflammation was also associated with deficient trophoblast invasion and SA remodeling, as well as with altered uteroplacental hemodynamics and placental nitrosative stress. Moreover, inflammation increased maternal mean arterial pressure (MAP) and was associated with renal structural alterations and proteinuria characteristic of PE. Finally, transdermal administration of the nitric oxide (NO) mimetic glyceryl trinitrate prevented altered uteroplacental perfusion, LPS-induced inflammation, placental nitrosative stress, renal structural and functional alterations, increase in MAP, and FGR. These findings demonstrate that maternal inflammation can lead to severe pregnancy complications via a mechanism that involves increased maternal levels of TNF. Our study provides a rationale for the use of antiinflammatory agents or NO-mimetics in the treatment and/or prevention of inflammation-associated pregnancy complications.
AuthorsTiziana Cotechini, Maria Komisarenko, Arissa Sperou, Shannyn Macdonald-Goodfellow, Michael A Adams, Charles H Graham
JournalThe Journal of experimental medicine (J Exp Med) Vol. 211 Issue 1 Pg. 165-79 (Jan 13 2014) ISSN: 1540-9538 [Electronic] United States
PMID24395887 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Creatinine
Topics
  • Analysis of Variance
  • Animals
  • Blood Cell Count
  • Blood Pressure (physiology)
  • Creatinine (urine)
  • Endometrium (blood supply)
  • Female
  • Fetal Growth Retardation (etiology)
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Inflammation (chemically induced, complications)
  • Kidney (ultrastructure)
  • Lipopolysaccharides (administration & dosage, toxicity)
  • Myocytes, Smooth Muscle (metabolism)
  • Pre-Eclampsia (etiology)
  • Pregnancy
  • Proteinuria (physiopathology)
  • Rats
  • Telemetry
  • Trophoblasts (metabolism)
  • Tumor Necrosis Factor-alpha (metabolism)
  • Ultrasonography, Doppler
  • Uterine Artery (pathology)

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