Intra-amniotic administration of lipopolysaccharide induces spontaneous preterm labor and birth in the absence of a body temperature change

Abstract

Objective: Intra-amniotic infection is associated with spontaneous preterm labor. In most cases, the infection is subclinical and bacteria are detected in the amniotic cavity rather than in the chorioamniotic membranes. The aims of this study were to establish a model of intra-amniotic lipopolysaccharide (LPS)-induced preterm labor/birth that resembles the subclinical syndrome and to compare this model to two established models of LPS-induced preterm labor/birth.

Methods: Pregnant B6 mice received an intra-amniotic, intra-uterine, or intra-peritoneal injection of LPS (100 ng/amniotic sac, 15 μg/25 μL, and 15 μg/200 μL respectively) or PBS (control). Following injection, body temperature (every two hours for a 12-h period), gestational age, and the rate of preterm labor/birth were recorded.

Results: An intra-amniotic injection of LPS resulted in preterm labor/birth [LPS 80 ± 24.79% (8/10) versus PBS 0% (0/8); p = 0.001] without causing maternal hypothermia. Intra-peritoneal [LPS 100% (8/8) versus PBS 0% (0/8); p < 0.001)] and intra-uterine [LPS 100% (8/8) versus PBS 28.57 ± 33.47% (2/7); p =0 .007] injections of LPS induced preterm labor/birth; yet, maternal hypothermia was observed.

Conclusion: Intra-amniotic injection of LPS induces preterm labor/birth in the absence of a body temperature change, which resembles the subclinical syndrome.

Keywords:

• Acute histologic chorioamnionitis
• clinical chorioamnionitis
• endotoxin
• fever
• funisitis
• hypothermia
• infection
• inflammation
• mouse
• parturition
• pregnancy
• prematurity

Acknowledgements

We thank Amy E. Furcron for her critical readings of the manuscript.

Disclosure statement

The authors report that they have no conflicts of interest.

Additional information

Funding

This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), and, in part, with federal funds from the NICHD/NIH/DHHS under Contract No. HHSN275201300006C. This research was also supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health.