Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

• Published in: International journal of molecular sciences Vol. 17; no. 10; p. 1610
• Main Authors: Yu, Hong-Ren, Tain, You-Lin, Sheen, Jiunn-Ming, Tiao, Mao-Meng, Chen, Chih-Cheng, Kuo, Ho-Chang, Hung, Pi-Lien, Hsieh, Kai-Sheng, Huang, Li-Tung
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.10.2016; MDPI
• Subjects: Adaptive Immunity; age-dependent; Aging; Animals; Blood Cells - cytology; Blood Cells - drug effects; Blood Cells - immunology; Body Weight; Cytokines - metabolism; Dexamethasone - toxicity; Diet, High-Fat; Down-Regulation - drug effects; Female; high-fat diet; histone modification; Histones - metabolism; Hormones; IFN-γ; Immune system; Interferon-gamma - genetics; Interferon-gamma - metabolism; Male; Metabolic syndrome; Pregnancy; Prenatal development; Prenatal Exposure Delayed Effects; prenatal glucocorticoid; Promoter Regions, Genetic; Rats; Rats, Sprague-Dawley; Spleen - cytology; Spleen - drug effects; Spleen - metabolism; Steroids; Th1 Cells - cytology; Th1 Cells - drug effects; Th1 Cells - metabolism; Th2 Cells - cytology; Th2 Cells - drug effects; Th2 Cells - metabolism; prenatal glucocorticoid; IFN-γ; histone modification; age-dependent; high-fat diet
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms17101610

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.