ingest cdrApp 2018-08-23T17:08:24.721Z d39a25df-af15-48e9-aec2-c9af81a997a2 modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-29T06:17:58.496Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-03-22T23:02:07.552Z Cassandra Meakin Author Department of Environmental Sciences and Engineering Gillings School of Global Public Health Inorganic Arsenic as an Endocrine Disruptor: Modulation of the Glucocorticoid Receptor Pathway and Implications on Placental Physiology Prenatal exposure to inorganic arsenic (iAs) has been associated with adverse developmental and reproductive outcomes, and may be tied to altered glucocorticoid receptor (GR) in the placenta. In this study, we investigated whether iAs exposure modulates GR signaling in placental cells. Trophoblast JEG-3 cells were exposed to environmentally-relevant doses of iAs and mRNA expression and DNA methylation were quantified. Results demonstrated that iAs exposure alters the expression of 12 GR-genes that play a role in fetal and placental development. Furthermore, supporting a role for the epigenome in control of this expression, the mRNA alterations were associated with changes in DNA methylation patterning in placental cells. The identified target genes have been implicated in associations with prenatal arsenic exposure, placental physiology, and fetal development. This study provides evidence of iAs as an endocrine disruptor and insight into the mechanisms by which prenatal iAs exposure induces adverse birth outcomes. Summer 2018 2018 Toxicology arsenic, epigenetics, glucocorticoid receptor eng Master of Science Thesis University of North Carolina at Chapel Hill Graduate School Degree granting institution Environmental Sciences and Engineering Rebecca Fry Thesis advisor Jill Stewart Thesis advisor Leena Nylander-French Thesis advisor text Cassandra Meakin Creator Department of Environmental Sciences and Engineering Gillings School of Global Public Health Inorganic Arsenic as an Endocrine Disruptor: Modulation of the Glucocorticoid Receptor Pathway and Implications on Placental Physiology Prenatal exposure to inorganic arsenic (iAs) has been associated with adverse developmental and reproductive outcomes, and may be tied to altered glucocorticoid receptor (GR) in the placenta. In this study, we investigated whether iAs exposure modulates GR signaling in placental cells. Trophoblast JEG-3 cells were exposed to environmentally-relevant doses of iAs and mRNA expression and DNA methylation were quantified. Results demonstrated that iAs exposure alters the expression of 12 GR-genes that play a role in fetal and placental development. Furthermore, supporting a role for the epigenome in control of this expression, the mRNA alterations were associated with changes in DNA methylation patterning in placental cells. The identified target genes have been implicated in associations with prenatal arsenic exposure, placental physiology, and fetal development. This study provides evidence of iAs as an endocrine disruptor and insight into the mechanisms by which prenatal iAs exposure induces adverse birth outcomes. Toxicology arsenic; epigenetics; glucocorticoid receptor Master of Science Masters Thesis University of North Carolina at Chapel Hill Graduate School Degree granting institution Environmental Sciences and Engineering Rebecca Fry Thesis advisor Jill Stewart Thesis advisor Leena Nylander-French Thesis advisor 2018 2018-08 eng text Cassandra Meakin Creator Department of Environmental Sciences and Engineering Gillings School of Global Public Health Prenatal exposure to inorganic arsenic (iAs) has been associated with adverse developmental and reproductive outcomes, and may be tied to altered glucocorticoid receptor (GR) in the placenta. In this study, we investigated whether iAs exposure modulates GR signaling in placental cells. Trophoblast JEG-3 cells were exposed to environmentally-relevant doses of iAs and mRNA expression and DNA methylation were quantified. Results demonstrated that iAs exposure alters the expression of 12 GR-genes that play a role in fetal and placental development. Furthermore, supporting a role for the epigenome in control of this expression, the mRNA alterations were associated with changes in DNA methylation patterning in placental cells. The identified target genes have been implicated in associations with prenatal arsenic exposure, placental physiology, and fetal development. This study provides evidence of iAs as an endocrine disruptor and insight into the mechanisms by which prenatal iAs exposure induces adverse birth outcomes. Toxicology arsenic; epigenetics; glucocorticoid receptor Master of Science Masters Thesis University of North Carolina at Chapel Hill Graduate School Degree granting institution Rebecca Fry Thesis advisor Jill Stewart Thesis advisor Leena Nylander-French Thesis advisor 2018 2018-08 eng text 2018-07-03T13:20:08Z proquest 2020-08-23T00:00:00 Inorganic Arsenic as an Endocrine Disruptor: Modulation of the Glucocorticoid Receptor Pathway and Implications on Placental Phy uuid:bd102313-cd7e-48dd-9a27-c1a5921f3690