Abstract
Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming.
Highlights
Prenatal glucocorticoid (GC) exposure has been shown to effectively stimulate the development of the fetal lung and decrease mortality and morbidity after birth [1]
A postnatal HF diet resulted in a heavier Body Weight (BW) than exposure to the vehicle and dexamethasone (Table 1)
We further found that postnatal HF exposure resulted in a lower spleen weight-to-BW ratio than in the vehicle group
Summary
Prenatal glucocorticoid (GC) exposure has been shown to effectively stimulate the development of the fetal lung and decrease mortality and morbidity after birth [1]. Overexposure to GC has been observed in prenatal stress, which can change the homeostasis of lipid and glucose metabolism in later life [2,3]. The modulating effect of prenatal GC on the developing immune system has been evaluated in several small series. In these limited studies on neonates to infants, prenatal exposure to GC seemed to have only a limited effect on the developing immune system [4,5,6]. Prolonged adverse effects on the immune system after prenatal GC treatment have been observed. We previously found that prenatal GC treatment reduced the capacity of adolescent rat splenocytes to produce tumor necrosis factor alpha (TNF-α) rather than interferon gamma (IFN-γ), and that prenatal
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