Maternal Poly (I:C)-Induced Placental Inflammation and Endocrine Dysfunction Are Associated with Disrupted...

Area of Science:

• Neuroscience
• Immunology
• Developmental Biology

Background:

• Maternal immune activation (MIA) is a known risk factor for Autism Spectrum Disorders (ASD).
• The placenta plays a crucial role in fetal brain development via immunological and hormonal regulation.
• Understanding how MIA affects placental function and subsequent neurodevelopment is critical.

Purpose of the Study:

• To investigate how MIA alters placental cytokine profiles, immune cell composition, and endocrine outputs.
• To examine the relationship between these placental changes and offspring neuroinflammation and neurogenesis.

Main Methods:

• Pregnant mice were exposed to polyinosinic:polycytidylic acid (poly(I:C)) to induce MIA.
• Placental macrophages, neutrophils, cytokines, and nerve growth factor (NGF) were analyzed.
• Offspring brains were assessed for microglial activity and neurogenesis markers.

Main Results:

• MIA led to increased placental monocytes, neutrophils, and pro-inflammatory cytokines in the placenta and amniotic fluid.
• Placental NGF levels were significantly reduced following MIA.
• MIA induced sustained microglial activation and disrupted cortical neurogenesis in offspring brains.

Conclusions:

• Heightened Th17 inflammatory signaling during MIA contributes to neurodevelopmental alterations.
• Impaired placental endocrine function, specifically reduced NGF, plays a role in dysregulated neurogenesis.
• These placental changes link MIA to altered fetal brain development and increased ASD risk.