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Updated: Dec 19, 2025
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
Fetal membrane extracellular vesicle profiling reveals distinct pathways induced by infection and inflammation in
Luis A Monsivais1, Samantha Sheller-Miller1, William Russell2
1Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine & Perinatal Research, The University of Texas Medical Branch at Galveston, Galveston, TX, USA.
Problem:
Fetal inflammatory signals can be propagated to maternal tissues to initiate labor via exosomes (extracellular vesicles; 30-150 nm). We tested the hypothesis that fetal membrane cells exposed to infectious and inflammatory mediators associated with preterm birth (PTB) produce exosomes with distinct protein cargo contents indicative of underlying pathobiology.
Methods Of Study:
Fetal membrane explants (FM) as well as primary amnion epithelial (AEC) and mesenchymal cells (AMC), and chorion cells (CC) from term deliveries were maintained in normal conditions (control) or exposed to LPS 100 ng/mL or TNF-α 50 ng/mL for 48 hours. Exosomes were isolated from media by differential centrifugation and size exclusion chromatography and characterized using cryo-electron microscopy (morphology), nanoparticle tracking analysis (size and quantity), Western blot (markers), and mass spectroscopy (cargo proteins). Ingenuity pathway analysis (IPA) determined pathways indicated by differentially expressed proteins.
Results:
Irrespective of source or treatment, exosomes were spherical, had similar size, quantities, and markers (ALIX, CD63, and CD81). However, exosome cargo proteins were different between FM and individual fetal membrane cell-derived exosomes in response to treatments. Several common proteins were seen; however, there are several unique proteins expressed by exosomes from different cell types in response to distinct stimuli indicative of unique pathways and physiological functions in cells.
Conclusions:
We demonstrate collective tissue and independent cell response reflected in exosomes in response to infectious and inflammatory stimuli. These cargoes determined underlying physiology and their potential in enhancing inflammation in a paracrine fashion.
Insights
Fetal membrane cells release exosomes that carry specific protein signals. These signals change based on inflammatory exposure, offering insights into preterm birth pathobiology.
Area of Science:
- Reproductive biology
- Cellular and molecular biology
- Biochemistry
Background:
- Fetal inflammatory signals can initiate labor via exosomes.
- Preterm birth (PTB) is associated with fetal inflammatory mediators.
- Exosomes are extracellular vesicles involved in intercellular communication.
Purpose of the Study:
- To test if fetal membrane cells exposed to infectious/inflammatory mediators produce exosomes with distinct protein cargo.
- To identify exosome cargo indicative of underlying pathobiology in PTB.
Main Methods:
- Fetal membrane explants and cells (amnion epithelial, mesenchymal, chorion) were treated with LPS or TNF-α.
- Exosomes were isolated using differential centrifugation and size exclusion chromatography.
- Exosomes were characterized by cryo-electron microscopy, nanoparticle tracking analysis, Western blot, and mass spectrometry.
Main Results:
- Exosomes were spherical with consistent size and markers (ALIX, CD63, CD81) across all conditions.
- Exosome cargo proteins differed significantly between fetal membrane explants and individual cell types post-treatment.
- Unique proteins in exosomes reflected distinct cellular responses to stimuli, indicating specific pathways.
Conclusions:
- Collective tissue and individual cell responses to inflammation are mirrored in exosome cargo.
- Exosome protein cargoes provide insights into underlying physiology and potential for inflammation enhancement.
