title: Glucocorticoids accelerate maturation of the heme pathway in fetal liver through effects on transcription and DNA methylation.
abstract: Glucocorticoids are widely used in threatened preterm labor to promote maturation in many organ systems in preterm babies and have significant beneficial effects on morbidity and mortality. We performed transcriptional profiling in fetal liver in a rat model of prenatal glucocorticoid exposure and identified marked gene expression changes in heme biosynthesis, utilization, and degradation pathways in late gestation. These changes in gene expression associated with alterations in DNA methylation and with a reduction in hepatic heme concentration. There were no persistent differences in gene expression, DNA methylation, or heme concentrations at 4 weeks of age, suggesting that these are transient effects. Our findings are consistent with glucocorticoid-induced accelerated maturation of the haematopoietic system and support the hypothesis that glucocorticoids can drive changes in gene expression in association with alterations in DNA methylation.
authors.affiliation: a University/BHF Center for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute , 47 Little France Crescent, Edinburgh , UK.
authors.forename: Batbayar
authors.initials: B
authors.lastname: Khulan
authors.affiliation: a University/BHF Center for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute , 47 Little France Crescent, Edinburgh , UK.
authors.forename: Lincoln
authors.initials: L
authors.lastname: Liu
authors.affiliation: a University/BHF Center for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute , 47 Little France Crescent, Edinburgh , UK.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Rose
authors.affiliation: a University/BHF Center for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute , 47 Little France Crescent, Edinburgh , UK.
authors.forename: Ashley K
authors.initials: AK
authors.lastname: Boyle
authors.affiliation: a University/BHF Center for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute , 47 Little France Crescent, Edinburgh , UK.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Manning
authors.affiliation: a University/BHF Center for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute , 47 Little France Crescent, Edinburgh , UK.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Drake
mesh_terms: D000818:Animals; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D044127:Epigenesis, Genetic; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D020869:Gene Expression Profiling; D005938:Glucocorticoids / Q000494:pharmacology*; D006418:Heme / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar; D059467:Transcriptome
chemical_list: D005938:Glucocorticoids; D006418:Heme; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D000090762:Cytochrome P-450 CYP2J2
keywords: DNA methylation; glucocorticoids; heme; liver; prenatal