Unraveling the molecular mechanisms of DIO2 regulation in response to cortisol in a human extravillous trophoblast cell line
Date of Award
Bachelor of Arts
Biochemistry & Molecular Biology
Maternal stress during pregnancy has been linked to increased risk for adverse pregnancy outcomes such as miscarriage, preeclampsia, and spontaneous abortion as well as increased risk for long term adverse metabolic, immune, and neurocognitive health outcomes for offspring. The placenta plays an important role in mediating the effects of maternal stress. In a mouse model of chronic maternal stress developed by our group, Deiodinase 2 (Dio2) was downregulated in the placenta of animals from stressed dams. DIO2 catalyzes the interconversion of circulating thyroid hormone, thyroxine (T4), to its active form, triiodothyronine (T3) and its downregulation is linked to potential adverse outcomes for pregnancy and fetal development. To unravel the mechanisms by which stress hormone (CORT) regulates expression of DIO2 in the placenta, I conducted experiments in a first trimester extravillous trophoblast cell line (Sw.71). Specifically, I investigated if CORT-induced DIO2 downregulation is directly mediated by the glucocorticoid receptor (GR) and if epigenetic modifications play a role in this regulation. I found that while CORT-induced DIO2 regulation is not dependent on DNA methylation, it is a GR mediated response. Using bioinformatic tools, I found three putative binding sequences for GR upstream of the DIO2 promoter, suggesting a direct binding mechanism of GR-mediated regulation of DIO2. I began to validate these sites using a chromatin immunoprecipitation (ChIP) assay to determine if GR directly binds upstream of DIO2 to further characterize the mechanism by which GR regulates DIO2 in extravillous trophoblasts.
Rahim, Rodaba, "Unraveling the molecular mechanisms of DIO2 regulation in response to cortisol in a human extravillous trophoblast cell line" (2022). Honors Theses. 301.
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Available for download on Friday, June 30, 2023