Exposure to excess glucocorticoids during fetal development has long-lasting physiological and behavioral consequences, although the mechanisms are poorly understood. The impact of prenatal glucocorticoids exposure on stress responses in juvenile and adult offspring implicates the developing @entity2339 as a target of adverse prenatal glucocorticoid action. Therefore, primary cultures of hypothalamic neural-progenitor/stem cells (NPSCs) derived from @entity19 embryos (embryonic day 14.5) were used to identify the glucocorticoid transcriptome in both males and females. NPSCs were treated with vehicle or the synthetic glucocorticoid @entity619 ( @entity9170 ; 100nM) for 4 hours and total RNA analyzed using RNA-Sequencing. Bioinformatic analysis demonstrated that primary hypothalamic NPSC cultures expressed relatively high levels of a number of genes regulating stem cell proliferation and hypothalamic progenitor function. Interesting, although these cells express glucocorticoid receptors (GRs), only low levels of sex- @entity479 receptors are expressed, which suggested that sex-specific differentially regulated genes identified are mediated by genetic and not hormonal influences. We also identified known or novel GR-target coding and noncoding genes that are either regulated equivalently in male and female NPSCs or differential responsiveness in one sex. Using gene ontology analysis, the top functional network identified was cell proliferation and using @entity1603 ( @entity1603 ) incorporation observed a reduction in proliferation of hypothalamic NPSCs after @entity619 treatment. Our studies provide the first characterization and description of glucocorticoid-regulated pathways in male and female embryonically derived hypothalamic NPSCs and identified GR-target genes during hypothalamic development. These findings may provide insight into potential mechanisms responsible for the long-term consequences of fetal glucocorticoid exposure in adulthood.

Research Resource: The XXXX Transcriptome in Hypothalamic Embryonic Neural Stem Cells.

@entity1603 :: ('MESH:D001973', 'Chemical') :: ['BrdU', 'bromodeoxyuridine'] @entity9170 :: ('D003907', 'Chemical') :: ['dex'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity619 :: ('MESH:D003907', 'Chemical') :: ['dexamethasone'] @entity2339 :: ('MESH:D007029', 'Disease') :: ['hypothalamus'] @entity479 :: ('D013256', 'Chemical') :: ['steroid']
@entity619 :: (MESH:D003907,Chemical) :: ['Dexamethasone']
