1. Glucocorticoids accelerate maturation of the heme pathway in fetal liver through effects on transcription and DNA methylation.
- Author
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Khulan B, Liu L, Rose CM, Boyle AK, Manning JR, and Drake AJ
- Subjects
- Animals, Cytochrome P-450 CYP2J2, Cytochrome P-450 Enzyme System genetics, Cytochrome P-450 Enzyme System metabolism, Dexamethasone pharmacology, Epigenesis, Genetic, Female, Gene Expression Profiling, Liver drug effects, Male, Pregnancy, Promoter Regions, Genetic, Rats, Rats, Wistar, Transcriptome, DNA Methylation drug effects, Fetal Development drug effects, Glucocorticoids pharmacology, Heme biosynthesis, Liver metabolism, Maternal Exposure
- 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.
- Published
- 2016
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