Prenatal dexamethasone exposure in rats results in long-term epigenetic histone modifications and tumour necrosis...

Area of Science:

• Immunology
• Developmental Biology
• Pharmacology

Background:

• Glucocorticoids (GCs) are used to accelerate fetal lung maturation before preterm birth.
• Limited data exists on the long-term effects of prenatal GC exposure on immune system development.
• Previous studies suggest minimal impact, but effects in later childhood remain unclear.

Purpose of the Study:

• To investigate the long-term impact of prenatal dexamethasone (DEX) exposure on immune programming in offspring.
• To determine if prenatal GC exposure affects immune responses and epigenetic modifications in adult rats.

Main Methods:

• Pregnant Sprague-Dawley rats received DEX or saline during late gestation.
• Offspring spleens were analyzed at early postnatal (day 7) and adult (day 120) stages.
• Gene expression of inflammation mediators and splenocyte cytokine production post-stimulation were assessed.

Main Results:

• Prenatal DEX reduced mRNA levels of MMP-9, TNF-α, and GM-CSF early post-birth.
• Adult rats exposed to prenatal DEX showed reduced TNF-α production upon stimulation.
• Decreased histone acetylation in the TNF-α promoter correlated with reduced TNF-α expression.

Conclusions:

• Prenatal DEX exposure exerts a profound and lasting influence on the developing immune system, extending into adulthood.
• Epigenetic modifications, specifically histone modifications in the TNF-α promoter, play a role in regulating immune responses following prenatal DEX exposure.