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Updated: Jun 3, 2026
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A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Intermediate Signaling Mechanisms Regulating Human Fetal Membrane Responses to Gram-Positive Bacterial Peptidoglycan
Hanah M Georges1, Abigail C Fischer1, Vikki M Abrahams1
1Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, USA.
Summary
Gram-positive bacteria trigger inflammation and membrane weakening in fetal membranes via TLR8 and miR-146a-3p signaling. This pathway involves NFκB and MAPK, contributing to chorioamnionitis pathogenesis.
Area of Science:
- Reproductive biology
- Immunology
- Molecular signaling
Background:
- Chorioamnionitis and preterm birth are major causes of neonatal complications.
- Understanding the molecular pathways in fetal membrane inflammation is crucial.
Purpose of the Study:
- Investigate the sequential microRNA activation of Toll-like receptor 8 (TLR8) signaling.
- Elucidate the role of NFκB and MAPK pathways in response to Gram-positive bacterial stimulation.
- Determine the impact on inflammation and fetal membrane weakening.
Main Methods:
- Human fetal membrane explants were stimulated with peptidoglycan (PDG), a TLR2 agonist.
- Inhibitors for TLR7, TLR8, NFκB, p38 MAPK, and ERK were used.
- Measurements included secreted factors (ELISA), microRNAs (RT-qPCR), and protein phosphorylation (Western blot).
Main Results:
- PDG induced miR-146a-3p and subsequent TLR8 activation in a NFκB-dependent manner.
- TLR8 activation led to increased IL-1β, IL-8, MMP1, MMP9, and PGE2.
- Inflammation and membrane weakening were dependent on NFκB, p38 MAPK, and ERK signaling (except for MMP9).
Conclusions:
- This study reveals novel molecular mechanisms in fetal membrane response to Gram-positive bacteria.
- The findings provide new insights into the pathogenesis of chorioamnionitis.
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