Unilateral uterine ischemia/reperfusion-induced bilateral fetal loss and fetal growth restriction in a murine model require intact complement component 5

J Reprod Immunol. 2012 Sep;95(1-2):27-35. doi: 10.1016/j.jri.2012.04.005. Epub 2012 Jun 9.

Abstract

The role of complement in ischemia/reperfusion-induced fetal growth restriction and fetal loss is unknown. C5-deficient or wild type timed-pregnant mice were subjected to unilateral uterine ischemia/reperfusion on gestation day 13, either by (1) partial flow restriction by right ovarian artery clamping for 30 min, or (2) total flow restriction by clamping both ovarian and uterine arteries for 5 min. Ischemia/reperfusion-challenged pregnancy outcomes were compared to sham-operated controls 5 days later. Ischemia/reperfusion-treated wild type mice exhibited significantly increased bilateral fetal loss, which was greater in total flow restriction than in partial flow restriction, and decreased fetal weights, which were the same in total flow restriction and partial flow restriction for the surviving fetuses. Placental weights were unchanged by treatments. Ischemia/reperfusion increased uterine, but not placental, myeloperoxidase activity, which correlated with fetal loss. In contrast, C5-deficient mice were protected from both fetal growth restriction and fetal loss, and exhibited no increase in myeloperoxidase activity. These results demonstrate that unilateral uterine ischemia/reperfusion results in bilateral fetal loss and fetal growth restriction, mediated by a systemic mechanism. In the current model, this pathological process is completely dependent on intact complement component 5.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Complement C5 / genetics
  • Complement C5 / immunology*
  • Complement C5 / metabolism
  • Disease Models, Animal
  • Enzyme Activation
  • Female
  • Fetal Death / genetics
  • Fetal Death / immunology*
  • Fetal Death / metabolism
  • Fetal Death / pathology
  • Fetal Growth Retardation / genetics
  • Fetal Growth Retardation / immunology*
  • Fetal Growth Retardation / metabolism
  • Fetal Growth Retardation / pathology
  • Humans
  • Mice
  • Mice, Mutant Strains
  • Peroxidase / genetics
  • Peroxidase / immunology
  • Peroxidase / metabolism
  • Placenta / blood supply
  • Placenta / immunology*
  • Placenta / metabolism
  • Placenta / pathology
  • Pregnancy
  • Reperfusion Injury / genetics
  • Reperfusion Injury / immunology*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Uterus / blood supply
  • Uterus / immunology*
  • Uterus / metabolism
  • Uterus / pathology

Substances

  • Complement C5
  • Peroxidase