Utilization of endoscopic inoculation in a mouse model of intrauterine infection-induced preterm birth: role of interleukin 1beta.
A novel murine model of intrauterine infection/inflammation-induced preterm birth based on direct endoscopic intracervical inoculation is described. Using this model, we investigated infection-induced premature pregnancy loss in normal and interleukin (IL) 1beta-deficient mice. Seventy-four CD-1, HS, C57BL/6J wild type (IL-1beta+/+), and C57BL/6J IL-1beta-deficient (IL-1beta-/-) mice were inoculated intracervically using a micro-endoscope, at a time corresponding to 70% of average gestation. Intracervical injection of lipopolysaccharide (LPS) or Escherichia coli reliably induced premature birth: 100% of mice intracervically injected with LPS and 92% of mice with a positive endometrial E. coli culture delivered prematurely within 36 h after inoculation. No losses were observed in mice inoculated with saline. Pregnancy loss was associated with increased uterine tissue cyclooxygenase-2 gene expression and uterine content of IL-1beta, tumor necrosis factor alpha, macrophage inflammatory protein-1alpha, and IL-6, as well as elevation of nuclear factor-kappaB activity in uterine tissues. Although IL-1beta-/- mice exhibited decreased uterine cytokine production in response to bacteria and LPS, IL-1beta deficiency did not affect the rate of pregnancy loss. This model using direct intracervical bacterial or LPS inoculation is useful for studying preterm pregnancy loss in genetically altered mice in order to develop novel interventions for infection-associated preterm labor.
Reznikov
L L
LL
Division of Infectious Diseases, University of Colorado Health SciencesCenter, Denver 80262, USA. leonid.reznikov@uchsc.edu
Fantuzzi
G
G
Selzman
C H
CH
Shames
B D
BD
Barton
H A
HA
Bell
H
H
McGregor
J A
JA
Dinarello
C A
CA
D000818:Animals; D051546:Cyclooxygenase 2; D004586:Electrophoresis; D004724:Endoscopy; D004926:Escherichia coli / Q000378:metabolism; D004927:Escherichia coli Infections / Q000150:complications* / Q000382:microbiology; D005260:Female; D007375:Interleukin-1 / Q000502:physiology*; D007527:Isoenzymes / Q000096:biosynthesis; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D007752:Obstetric Labor, Premature / Q000209:etiology*; D010544:Peroxidases / Q000096:biosynthesis; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014591:Uterine Diseases / Q000150:complications* / Q000382:microbiology
D007375:Interleukin-1; D007527:Isoenzymes; D016328:NF-kappa B; D010544:Peroxidases; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases