Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats.
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.
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. yuu2004taiwan@yahoo.com.tw.
Hong-Ren
HR
Yu
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. tainyl@hotmail.com.
You-Lin
YL
Tain
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. ray.sheen@gmail.com.
Jiunn-Ming
JM
Sheen
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. pc006581@yahoo.com.tw.
Mao-Meng
MM
Tiao
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. charllysc@yahoo.com.tw.
Chih-Cheng
CC
Chen
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. erickuo48@yahoo.com.tw.
Ho-Chang
HC
Kuo
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. flora1402@cgmh.org.tw.
Pi-Lien
PL
Hung
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. kshsieh@adm.cgmh.org.tw.
Kai-Sheng
KS
Hsieh
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. huang_li@pie.com.tw.
Li-Tung
LT
Huang
D056704:Adaptive Immunity; D000375:Aging; D000818:Animals; D001773:Blood Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D001835:Body Weight; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000633:toxicity*; D059305:Diet, High-Fat; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D006657:Histones / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; D006657:Histones; D003907:Dexamethasone; D007371:Interferon-gamma
IFN-γ; age-dependent; high-fat diet; histone modification; prenatal glucocorticoid
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