Related Experiment Video

Updated: Jun 3, 2026

A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
08:50

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.

American Journal of Reproductive Immunology (New York, N.Y. : 1989)
|May 28, 2025
PubMed
Abstract

Insights

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.
Keywords:
Toll‐like receptor 8bacteriachorioamnionitisfetal membraneinfectioninflammationmicroRNA

More Related Videos

Isolation of Leukocytes from the Murine Tissues at the Maternal-Fetal Interface07:51

Isolation of Leukocytes from the Murine Tissues at the Maternal-Fetal Interface

Published on: May 21, 2015

Related Concept Videos

Transcytosis of IgG01:15

Transcytosis of IgG

Transcytosis is the process in which molecules are internalized by endocytosis, transported across the cell, and released through exocytosis from the opposite end of the cell. Molecules such as insulin, immunoglobulins, and certain nutrients are transferred through the recycling endosomes by recycling and transcytosis.
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
Development of Immunocompetence01:22

Development of Immunocompetence

The initiation of cell-mediated immunity can be observed as early as the third month of fetal growth, with active antibody-mediated immunity following approximately one month later.
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
Regulation of Bacterial Virulence01:28

Regulation of Bacterial Virulence

Pathogenic bacteria employ a range of regulatory mechanisms to modulate the expression of virulence genes in response to environmental and host-derived signals. These mechanisms ensure that virulence factors are expressed only under favorable conditions, thereby optimizing infection and survival strategies.Mechanisms of Virulence RegulationKey regulatory strategies include:Two-Component Systems: These consist of a membrane-bound sensor kinase and a cytoplasmic response regulator. Environmental...
Inhibitors of Gram-positive Cell Wall Synthesis01:23

Inhibitors of Gram-positive Cell Wall Synthesis

Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
Peptidoglycan Synthesis01:28

Peptidoglycan Synthesis

Structure of PeptidoglycanPeptidoglycan is a vital structural component of the bacterial cell wall, providing mechanical strength and shape to the cell. It consists of repeating units of two sugars—N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM)—linked by β-1,4 glycosidic bonds. These sugar chains are cross-linked by short peptide chains, forming a mesh-like polymer that surrounds the bacterial plasma membrane.Cytoplasmic Phase – Precursor SynthesisPeptidoglycan biosynthesis begins in...
Types of Signaling Molecules01:32

Types of Signaling Molecules

In multicellular organisms, many molecules transmit signals between cells to pass information. These signals vary in complexity and include small peptides, nucleotides, steroids, fatty acid derivatives, and dissolved gases such as nitric oxide. Some signaling molecules diffuse through the plasma membrane to act locally between neighboring cells or travel long distances. Others remain attached to the cell surface, transmitting information to other cells only when they make contact. In some...