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Utilization of Endoscopic Inoculation in a Mouse Model of Intrauterine Infection-Induced Preterm Birth: Role of Interleukin 1ß¹

^a Division of Infectious Diseases and ^b Department of Surgery, University of Colorado Health Sciences Center, Denver, Colorado 80262 ^c Embryology Associates, Inc., Boulder, Colorado 80303 ^d Department of Obstetrics and Gynecology, Denver General Hospital, Denver, Colorado 80204

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) 1ß-deficient mice. Seventy-four CD-1, HS, C57BL/6J wild type (IL-1ß^+/+), and C57BL/6J IL-1ß-deficient (IL-1ß^-/-) 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-1ß, tumor necrosis factor , macrophage inflammatory protein-1, and IL-6, as well as elevation of nuclear factor-B activity in uterine tissues. Although IL-1ß^-/- mice exhibited decreased uterine cytokine production in response to bacteria and LPS, IL-1ß 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.

¹ This work was supported by grants from the NIH (AI-15614 to C.A.D. and AI-2532359 to L.L.R.) and Colorado Cancer Center (CA-46943 to C.A.D.).

² Correspondence: Leonid L. Reznikov, Univ. Colorado Health Sciences Center, Division Infectious Diseases, Campus Box B-168, 4200 East Ninth Ave., BRB 401, Denver, CO 80220. FAX: 303 315 8054; leonid.reznikov{at}uchsc.edu

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