title: Prenatal dexamethasone exposure in rats results in long-term epigenetic histone modifications and tumour necrosis factor-α production decrease.
abstract: Glucocorticoid (GC) is often given when preterm delivery is expected. This treatment is successful in stimulating the development of the fetal lung. However, reports and related research regarding the prolonged effects of prenatal GC on the development of immunity are very limited. Some data, derived from infants whose mothers were given immunosuppressants during pregnancy for the treatment of autoimmune disorders, suggest that prenatal exposure to GC may have only a limited effect on the development of the immune system. What is unknown is whether the immune modulation effects of prenatal GC might appear at a later childhood stage and beyond. Here we evaluated the immune programming influenced by prenatal GC. Pregnant Sprague-Dawley rats received dexamethasone (DEX; 0.1 mg/kg/day) or saline at gestational days 14-20. Male offspring were killed at day 7 or day 120 after birth. Spleens were collected for immune study. Of the inflammation mediators, matrix metalloproteinase-9, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor mRNAs decreased in the prenatal DEX group at an early stage after birth. Upon concanavalin A stimulation, prenatal DEX treatment reduced TNF-α production, but not interferon-γ production, by splenocytes at day 120 after birth compared with the vehicle group. Decreased levels of active chromatin signs (acetylation of histone H3 lysines, H3K4me1/3, and H3K36me3) in TNF-α promoter were compatible with the expressions of TNF-α. Our results suggest that prenatal DEX has a profound and lasting impact on the developing immune system even to the adult stage. Epigenetic histone modifications regulate TNF-α expression following prenatal DEX in rats.
authors: Department of Paediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Centre, Graduate Insititute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Hong-Ren
authors: HR
authors: Yu
authors: Ho-Chang
authors: HC
authors: Kuo
authors: Chih-Cheng
authors: CC
authors: Chen
authors: Jiunn-Ming
authors: JM
authors: Sheen
authors: Mao-Meng
authors: MM
authors: Tiao
authors: Yu-Chieh
authors: YC
authors: Chen
authors: Kow-Aung
authors: KA
authors: Chang
authors: You-Lin
authors: YL
authors: Tain
authors: Li-Tung
authors: LT
authors: Huang
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D051548:Histone Acetyltransferases / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy; D011256:Pregnancy Outcome; D064546:Protein Kinase C beta / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013163:Splenomegaly / Q000139:chemically induced; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D006657:Histones; D018836:Inflammation Mediators; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D051548:Histone Acetyltransferases; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D006655:Histone Deacetylases
keywords: epigenetic; prenatal glucocorticoid; tumour necrosis factor-α