title: Prenatal Dexamethasone Exposure Increases the Susceptibility to Autoimmunity in Offspring Rats by Epigenetic Programing of Glucocorticoid Receptor.
abstract: Objective. Prenatal glucocorticoids (GC) can induce long term effects on offspring health. However, reports and related studies regarding the prolonged effects of prenatal GC on the development of autoimmunity are limited. Here, we aimed to explore the immunological effects of dexamethasone (DEX) exposure on young adults and whether glucocorticoid receptor (GR) is involved in this process.Methods. Wistar rats were given DEX during pregnancy. Susceptibility to autoimmunity in offspring was assessed using experimental autoimmune encephalomyelitis (EAE) and adjuvant-induced arthritis (AIA) animal models. To reveal the possible mechanism, glucocorticoid response, GR expression, and methylation status were measured in peripheral blood mononuclear cells (PBMCs).Results. Our results showed that the DEX-treated rats had greater susceptibility to EAE (100% versus 62.5%,P< 0.05) and AIA (63.6% versus 0%,P< 0.05) than saline control group. Glucocorticoid response and GR expression were decreased in DEX rats. Significant difference was also found in the methylation levels of GR exon 1-10 to exon 1-11 region.Conclusions. Prenatal DEX administration increases the susceptibility to autoimmune diseases, which is potentially mediated by programming GR methylation status and glucocorticoid sensitivity.
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan Road 2, Guangzhou 510080, China; Department of Laboratory Medicine, Huangpu Division, The First Affiliated Hospital of Sun Yat-sen University, Huangpu East Road 3762, Guangdong, Guangzhou 510700, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan 430000, China; Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan 430000, China.
authors.forename: Xiaoyan
authors.identifier: 0000-0002-8193-2410
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan Road 2, Guangzhou 510080, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ouyang
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan Road 2, Guangzhou 510080, China.
authors.forename: Renfeng
authors.initials: R
authors.lastname: Xie
authors.affiliation: Department of Laboratory Medicine, Sun Yat-sen University Cancer Center, Dongfeng East Road 651, Guangzhou 510060, China.
authors.forename: Xueping
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan Road 2, Guangzhou 510080, China.
authors.forename: Peisong
authors.identifier: 0000-0003-0640-3663
authors.initials: P
authors.lastname: Chen
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D003907:Dexamethasone / Q000633:toxicity*; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D005938:Glucocorticoids / Q000633:toxicity*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000276:immunology
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone