Maternal Allergic Asthma Induces Prenatal Neuroinflammation

Area of Science:

• Neuroscience
• Immunology
• Developmental Biology

Background:

• Autism spectrum disorder (ASD) diagnosis rates are increasing.
• Epidemiological studies suggest a link between maternal allergic asthma and increased ASD risk.
• A lack of robust laboratory models hinders mechanistic research into this association.

Purpose of the Study:

• To investigate the impact of maternal allergic asthma on the maternal environment, specifically inflammatory markers in the placenta and fetal brain.
• To elucidate the role of neuroinflammation in fetuses exposed to maternal asthma during gestation.
• To establish and utilize a novel mouse model of maternal asthma-allergy (MAA) for mechanistic studies.

Main Methods:

• Developed a mouse model of maternal asthma-allergy (MAA) by exposing pregnant mice to ovalbumin (OVA).
• Collected placental and fetal brain tissues at specific gestational days (GD9.5, 12.5, 17.5) after OVA or PBS exposure.
• Measured changes in cytokine levels using a Luminex bead-based multiplex assay.

Main Results:

• Placental tissues showed decreased levels of interleukin-17 (IL-17) in both male and female offspring.
• Sex-dependent alterations in placental chemokines were observed, including decreased monocyte chemoattractant protein 1 (MCP-1) in females.
• Fetal brains exhibited elevated pro-inflammatory cytokines (IFN-γ, IL-1α, IL-6, TNFα) and decreased IL-9, with sex-specific differences in other chemokine levels.

Conclusions:

• Repeated exposure to allergic asthma during pregnancy alters cytokine expression in the fetal environment.
• These alterations occur in a sex-dependent manner, impacting fetal brain neuroinflammation.
• The findings suggest a potential mechanism linking maternal allergic asthma to neurodevelopmental alterations in offspring.