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Updated: May 14, 2026
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
Inhibition of endotoxin-induced perinatal asthma protection by pollutants in an experimental mouse model
M Reiprich1, S Rudzok, N Schütze
1Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig-Halle, Leipzig, Germany.
Insights
Early exposure to microbial compounds like endotoxin (lipopolysaccharide, LPS) protects offspring from asthma. However, prenatal exposure to pollutants such as mycotoxins or diesel exhaust particles (DEP) blocks this protective effect, increasing asthma risk.
Area of Science:
- Environmental Health
- Immunology
- Perinatal Medicine
Background:
- Increasing asthma prevalence necessitates novel prevention strategies.
- Early-life microbial exposure may protect against asthma development.
- The impact of co-exposures to pollutants on this protection is unknown.
Purpose of the Study:
- To investigate if perinatal exposure to endotoxin (lipopolysaccharide, LPS) protects offspring from asthma.
- To determine if co-exposure to mycotoxins or diesel exhaust particles (DEP) during pregnancy interferes with this protection.
Main Methods:
- Pregnant mice were exposed to aerosolized LPS.
- Offspring were exposed to LPS and ovalbumin (OVA) for asthma induction.
- Some pregnant mice were co-exposed to mycotoxins or DEP.
Main Results:
- Perinatal LPS exposure protected offspring from an asthma-like phenotype.
- Co-exposure to mycotoxins or DEP during pregnancy abolished LPS-induced protection, leading to airway inflammation and hyperactivity.
- The protective effect of LPS was IFN-gamma dependent and involved histone acetylation; N-acetylcysteine reversed pollutant effects.
Conclusions:
- Prenatal exposure to pollutants can negate the asthma-protective effects of early-life microbial compound exposure.
- This inhibition by pollutants may lead to the development of allergic asthma in offspring.
- Intervention with antioxidants may mitigate pollutant-induced increases in asthma risk.
Background:
One of the most promising strategies to face the increasing asthma prevalence and to prevent disease development might be an early contact with microbial compounds. However, little is known about an interaction between an early-life contact to microbial compounds leading to asthma protection in the offspring and a co-exposure to allergy-promoting pollutants.
Methods:
Pregnant BALB/c mice were repeatedly exposed to aerosolized endotoxin (lipopolysaccharide, LPS). The offspring was further exposed to aerosolized LPS before allergen sensitization with ovalbumin (OVA). Some of the mice were co-exposed to mycotoxins or diesel exhaust particles (DEP) during pregnancy. The 6-week-old offspring was immunized with OVA and analyzed in a murine asthma model.
Results:
While the offspring of naïve mothers developed an asthma-like phenotype, the offspring of mice perinatally exposed to LPS was significantly protected. Co-exposure of mice to mycotoxins or DEP during pregnancy inhibited the LPS-induced protection leading to the development of eosinophilic airway inflammation, airway hyperactivity, and increased antigen-specific IgE levels in the offspring. Furthermore, the asthma-preventive effect of perinatal LPS exposure was IFN-gamma dependent. Additionally, the IFN-gamma promoter of CD4+ T cells in the LPS-exposed offspring revealed a significant protection against loss of histone 4 acetylation, which was abolished after prenatal co-exposure to pollutants. Prenatal treatment of mice with the antioxidant N-acetylcysteine reversed the pollutant-induced increased asthma risk in the offspring.
Conclusion:
Our results show that exposure to pollutants during pregnancy may cause the development of allergic asthma in the offspring by inhibiting the endotoxin-induced perinatal asthma protection.
