The Local and Systemic Immune Response to Intrauterine LPS in the Prepartum Mouse

Area of Science:

• Reproductive Biology
• Immunology
• Perinatology

Background:

• Inflammation is critical in term and preterm labor (PTL).
• Intrauterine lipopolysaccharide (LPS) models inflammation-induced pregnancy complications like PTL.
• The role of LPS-induced inflammatory cell activation in labor onset and fetal demise remains unclear.

Purpose of the Study:

• To investigate the role of intrauterine LPS-induced inflammatory cell activation in labor onset and fetal demise.
• To elucidate the mechanisms by which LPS influences parturition and fetal outcomes.

Main Methods:

• A mouse model of PTL using intrauterine LPS injection (10 μg, serotype 0111:B4) at E16.
• Flow cytometry to analyze leukocyte infiltration and inflammatory markers.
• Analysis of myometrial activation of NFκB and MAPK/AP-1 pathways.
• Assessment of cytokine and chemokine levels.

Main Results:

• LPS induced PTL at 12.7 hours with 85% fetal demise.
• A dramatic systemic inflammatory response was observed, with leukocyte infiltration into maternal lung and liver.
• Myometrial activation of NFκB and MAPK/AP-1 pathways increased with parturition onset.
• Limited inflammatory cell infiltration into the myometrium or placenta was noted.

Conclusions:

• Intrauterine LPS induces parturition directly, independent of myometrial inflammatory cell infiltration.
• Fetal demise occurs without evidence of fetal inflammation.
• LPS provokes a marked local and systemic inflammatory response but with limited myometrial or placental infiltration.