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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
Immunological characterization of superantigen-induced intrauterine fetal and newborn death
Eriko Takei1, Hidekazu Tamauchi, Hiroko Maruyama
1Department of Obstetrics and Gynecology, Kitasato University School of Medicine, Kitasato 1-15-1, Sagamihara, Kanagawa 228-8555, Japan. eriko@med.kitasato-u.ac.jp
Problem:
The present study characterizes the immunological responses induced by superantigen and the underlying pathological mechanism using T-cell receptor-transgenic mice (TCR-Tg) to enable the ligand toxic shock syndrome toxin-1 (TSST-1) to induce a cytokine storm.
Method Of Study:
Three kinds of pregnant mice which could respond to TSST-1 at various levels were injected with TSST-1 on gestation day 17.5 and then the incidence of fetal/newborn death, production of cytokines including serum interleukin-2 (IL-2) and the histological status of the placenta were examined on day 18.5.
Results:
The incidence of fetal/newborn death and the concentrations of cytokines such as IL-2 were higher in TCR-Tg mother than those in other strains of mice. Pathological examinations revealed that the placenta was congestive and apoptotic in TCR-Tg mice.
Conclusions:
Superantigen injection into pregnant mice appears to increase the incidence of fetal/newborn death through an IL-2-dependent immunological pathway.
Insights
Superantigen exposure during pregnancy, specifically toxic shock syndrome toxin-1 (TSST-1), increases fetal and newborn deaths. This is linked to elevated interleukin-2 (IL-2) and placental damage in susceptible mice.
Area of Science:
- Immunology
- Toxicology
- Reproductive Biology
Background:
- Superantigens, like TSST-1, can trigger potent immune responses.
- Cytokine storms are associated with severe pathological outcomes.
- Understanding maternal immune responses to toxins is crucial for fetal well-being.
Purpose of the Study:
- To investigate the immunological and pathological effects of TSST-1 in pregnant mice.
- To elucidate the role of T-cell receptor-transgenic (TCR-Tg) mice in modeling superantigen-induced toxicity.
- To characterize the cytokine storm and its impact on pregnancy.
Main Methods:
- TSST-1 was administered to pregnant mice with varying sensitivities.
- Fetal/newborn death rates were recorded.
- Serum cytokine levels (e.g., IL-2) and placental histology were analyzed.
Main Results:
- TCR-Tg mice exhibited significantly higher fetal/newborn death rates after TSST-1 exposure.
- Elevated serum IL-2 concentrations were observed in TCR-Tg mothers.
- Placental examination revealed congestion and apoptosis in TCR-Tg mice.
Conclusions:
- TSST-1 administration during pregnancy increases fetal/newborn mortality.
- The observed increase in mortality is mediated by an IL-2-dependent immune pathway.
- TCR-Tg mice serve as a valuable model for studying superantigen-induced pregnancy complications.
