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Updated: May 30, 2026
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Modeling Ascending Vaginal Infection, Preterm Birth, and Neonatal Morbidity in Mice
Published on: October 10, 2025
Complement activation triggers metalloproteinases release inducing cervical remodeling and preterm birth in mice
Juan M Gonzalez1, Claus-Werner Franzke, Fengyuan Yang
1Perinatology Research Branch, National Institutes of Health, National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
The American Journal of Pathology
|August 2, 2011
Summary
Complement activation contributes to preterm delivery by promoting cervical remodeling. Blocking complement receptor C5a or using progesterone may prevent preterm birth.
Area of Science:
- Reproductive biology
- Immunology
- Biochemistry
Background:
- Inflammation is a known risk factor for preterm delivery (PTD).
- The role of the complement system, particularly complement activation, in PTD and associated cervical remodeling is not fully understood.
Purpose of the Study:
- To investigate the role of complement activation in inflammation-induced cervical remodeling and PTD.
- To determine the involvement of complement receptor C5a (C5aR) and macrophages in these processes.
- To explore the potential therapeutic effects of complement inhibition and progesterone supplementation.
Main Methods:
- Utilized two mouse models of inflammation-induced PTD (lipopolysaccharide and RU486 administration).
- Assessed cervical C3 deposition, macrophage infiltration, serum complement split products (C3adesArg, C5adesArg), collagen degradation, matrix metalloproteinase 9 (MMP-9) activity, and cervical tissue distensibility.
- Employed complement receptor C5a-deficient mice and macrophage depletion strategies.
- Conducted in vitro studies on macrophage responses to C5a and the effect of progesterone on C5aR expression and MMP-9 release.
Main Results:
- Both PTD models exhibited increased cervical C3 deposition, macrophage infiltration, and elevated serum C3adesArg and C5adesArg levels.
- Significant increases in collagen degradation, MMP-9 activity, and cervical distensibility were observed in both models.
- Mice deficient in C5aR did not exhibit increased MMP-9 activity, cervical remodeling, or PTD in response to LPS or RU486.
- In vitro, macrophages released MMP-9 upon C5a stimulation.
- Progesterone reduced C5aR on macrophages, inhibited MMP-9 release, and prevented PTD.
- Macrophage depletion also prevented cervical remodeling and PTD in LPS-treated mice.
Conclusions:
- C5a-C5aR interaction is crucial for macrophage-mediated MMP-9 release, leading to cervical remodeling and PTD.
- Complement activation, specifically via C5aR, plays a significant role in inflammation-induced preterm delivery.
- Complement inhibition and progesterone supplementation represent potential therapeutic strategies for preventing PTD.
