Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent...

Area of Science:

• Endocrinology
• Immunology
• Developmental Biology

Background:

• Prenatal glucocorticoid (GC) exposure disrupts neuroendocrine metabolism and increases susceptibility to metabolic syndrome.
• High-fat (HF) diets are significant environmental contributors to metabolic syndrome development.

Purpose of the Study:

• To investigate the combined effects of prenatal GC exposure and postnatal HF diet on immune programming in rat offspring.
• To elucidate the underlying epigenetic mechanisms, specifically histone modifications, influencing immune responses.

Main Methods:

• Pregnant Sprague-Dawley rats received dexamethasone or saline injections during gestation.
• Offspring were divided into four groups: control, prenatal dexamethasone, postnatal HF diet, and combined exposure.
• Adaptive immune function, including interferon gamma (IFN-γ) production and histone modifications at the IFN-γ promoter, was assessed.

Main Results:

• The combined prenatal GC and postnatal HF diet group (DHF) exhibited significantly lower IFN-γ production by splenocytes at postnatal day 120.
• Decreased H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with reduced IFN-γ production.
• Impaired IFN-γ production and aberrant histone modifications were observed in the DHF group, with resilience noted at postnatal day 180.

Conclusions:

• Prenatal GC exposure and a postnatal HF diet synergistically impair fetal immune programming by decreasing IFN-γ production.
• This immune dysregulation is mediated by site-specific and age-dependent epigenetic modifications at the IFN-γ promoter.
• These findings highlight a critical window during development where environmental factors can permanently alter immune function.