Utilization of endoscopic inoculation in a mouse model of intrauterine infection-induced preterm birth: Role of interleukin 1 beta

A novel murine model of intrauterine infection/inflammation-induced preterm birth based on direct endoscopic intracervical inoculation is described. U sing this model, we investigated infection-induced premature pregnancy loss in normal and interleukin (IL) 1 beta p-deficient mice. Seventy-four CD-1, HS, C57BL/6J wild type (IL-1 beta(+/+)), and C57BL/6J IL-1 beta-deficient (IL-1 beta(-/-)) mice were inoculated intracervically using a micro-endosco pe, at a time corresponding to 70% of average gestation. Intracervical inje ction of lipopolysaccharide (LPS) or Escherichia coli reliably induced prem ature birth: 100% of mice intracervically injected with LPS and 92% of mice with a positive endometrial E. coli culture delivered prematurely within 3 6 h after inoculation. No losses were observed in mice inoculated with sali ne. Pregnancy loss was associated with increased uterine tissue cyclooxygen ase-2 gene expression and uterine content of IL-1 beta, tumor necrosis fact or alpha, macrophage inflammatory protein-1 alpha, and IL-6, as well as ele vation of nuclear factor-kappa B activity in uterine tissues. Although IL-1 beta(-/-) mice exhibited decreased uterine cytokine production in response to bacteria and LPS, IL-1 beta deficiency did not affect the rate of pregn ancy loss. This model using direct intracervical bacterial or LPS inoculati on is useful for studying preterm pregnancy loss in genetically altered mic e in order to develop novel interventions for infection-associated preterm labor.