Maternal/fetal mortality and fetal growth restriction: role of nitric oxide and virulence factors in intrauterine infection in rats

Am J Obstet Gynecol. 2011 Jul;205(1):83.e1-7. doi: 10.1016/j.ajog.2011.02.049. Epub 2011 Feb 23.

Abstract

Objective: The mechanism of infection-related deaths of pregnant rats and intrauterine growth restriction are not understood. We assessed whether nitric oxide (NO) has differential effects on infection with Escherichia coli Dr/Afa mutants that lack either AfaE or AfaD invasins.

Study design: Sprague-Dawley rats were infected intrauterinally with the clinical strain of E coli AfaE(+)D(+) or 1 of its isogenic mutants in the presence or absence of the NO synthesis inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). Maternal/fetal mortality rates, fetoplacental weight, and infection rates were evaluated.

Results: Maternal and/or fetal death was associated with the presence of at least 1 virulence factor (AfaE(+)D(+)>AfaE(+)D(-)>AfaE(-)D(+)) and was increased by L-NAME treatment. The fetal and placental weights were lower than controls and were further reduced by L-NAME treatment.

Conclusion: These results demonstrate that NO enhanced AfaE- and AfaD-mediated virulence and plays an important role in Dr/Afa(+)E coli gestational tropism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Enzyme Inhibitors / pharmacology
  • Escherichia coli / drug effects
  • Escherichia coli Infections / chemically induced
  • Escherichia coli Infections / mortality
  • Female
  • Fetal Growth Retardation / chemically induced
  • Fetal Growth Retardation / microbiology
  • Fetal Growth Retardation / mortality*
  • Fetal Mortality*
  • Fetus / drug effects
  • Maternal Mortality*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Pregnancy
  • Pregnancy Complications, Infectious / chemically induced
  • Rats
  • Rats, Sprague-Dawley
  • Uterine Diseases / chemically induced
  • Uterine Diseases / microbiology
  • Uterine Diseases / mortality
  • Virulence Factors / metabolism*

Substances

  • Enzyme Inhibitors
  • Virulence Factors
  • Nitric Oxide
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester