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Updated: Aug 19, 2026
A Mouse Fetal Skin Model of Scarless Wound Repair
Published on: January 16, 2015
Healing of Preterm Ruptured Fetal Membranes
Haruta Mogami1, Annavarapu Hari Kishore1, Yucel Akgul2
1The Cecil H. and Ida Green Center for Reproductive Biological Sciences, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Abstract:
Preterm premature rupture of membrane (pPROM) is associated with 30-40% of preterm births. Infection is considered a leading cause of pPROM due to increased levels of proinflammatory cytokines in amniotic fluid. Only 30%, however, are positive for microbial organisms by amniotic fluid culture. Interestingly, in some pregnancies complicated by preterm premature rupture of membranes (pPROM), membranes heal spontaneously and pregnancy continues until term. Here, we investigated mechanisms of amnion healing. Using a preclinical mouse model, we found that small ruptures of the fetal membrane closed within 72 h whereas healing of large ruptures was only 40%. Small rupture induced transient upregulation of cytokines whereas large ruptures elicited sustained upregulation of proinflammatory cytokines in the fetal membranes. Fetal macrophages from amniotic fluid were recruited to the wounded amnion where macrophage adhesion molecules were highly expressed. Recruited macrophages released limited and well-localized amounts of IL-1β and TNF which facilitated epithelial-mesenchymal transition (EMT) and epithelial cell migration. Arg1 + macrophages dominated within 24 h. Migration and healing of the amnion mesenchymal compartment, however, remained compromised. These findings provide novel insights regarding unique healing mechanisms of amnion.
Insights
Preterm premature rupture of membranes (pPROM) can heal spontaneously. Macrophages aid healing by promoting epithelial cell migration, but mesenchymal healing remains limited in a mouse model.
Area of Science:
- Reproductive biology
- Wound healing mechanisms
- Obstetrics
Background:
- Preterm premature rupture of membranes (pPROM) contributes significantly to preterm births.
- Infection is a suspected cause of pPROM, but microbial evidence is often lacking.
- Spontaneous amnion healing occurs in some pPROM cases, prompting investigation into its mechanisms.
Purpose of the Study:
- To investigate the mechanisms underlying amnion healing following rupture.
- To differentiate healing responses based on rupture size in a preclinical model.
Main Methods:
- Utilized a preclinical mouse model to simulate amnion rupture.
- Analyzed cytokine profiles and macrophage recruitment to wounded fetal membranes.
- Assessed epithelial-mesenchymal transition (EMT) and cell migration.
Main Results:
- Small amnion ruptures healed within 72 hours; large ruptures showed only 40% healing.
- Small ruptures induced transient cytokine upregulation, while large ruptures caused sustained inflammation.
- Macrophages were recruited to wounded amnion, expressing adhesion molecules and releasing IL-1β and TNF, promoting epithelial healing.
- Arg1+ macrophages predominated within 24 hours, but mesenchymal healing remained impaired.
Conclusions:
- Macrophage-mediated epithelial repair is a key component of amnion healing.
- The extent of inflammation correlates with rupture size and impacts healing outcomes.
- Mesenchymal compartment healing presents a significant limitation in amnion repair.
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