Date of Award

Spring 5-9-2022

Document Type

Thesis

Degree Name

Bachelor of Arts

Department

Biochemistry & Molecular Biology

First Advisor

Arianna Smith, Ph.D.

Abstract

Prenatal maternal stress has been associated with a variety of adverse pregnancy outcomes ranging from immediate effects such as low birth weight and miscarriage to long-term effects including increased susceptibility to immune, metabolic, and neurocognitive disorders in children. The placenta acts as an intermediary for maternal/fetal communication and is subject to molecular changes following prolonged exposure to maternal stress. To explore how stress during pregnancy alters the placenta, we analyzed data from an RNA-seq experiment using a mouse model of prenatal stress during late pregnancy. Type II iodothyronine deiodinase 2 (Dio2) was significantly downregulated in placenta collected from CORT-treated dams relative to placenta collected from vehicle-treated dams. Dio2 is an integral component of the thyroid hormone signaling pathway, responsible for converting the inactive form of the thyroid hormone, thyroxine (T4), into the biologically active form, triiodothyronine (T3). Using immunohistochemistry, we identified DIO2 expression in glycogen cells and trophoblast giant cells in the maternal decidua and junctional zone, and within the chorionic plate of the placenta. To evaluate the effect of a reduction of Dio2 expression on thyroid hormone bioavailability, we measured placental thyroid hormone abundance using ELISAs. We saw a significant reduction of T3 levels in female placenta collected from CORT-treated dams, and a subsequent decrease in female fetal T3 serum and 7-day old neonate serum. T3 levels in CORT-treated male placenta did not reach significance. These reductions were independent of changes in placental T4 levels. Additionally, we did not observe a change in T4 levels in pregnant dams. In sum, these data suggest maternal stress during pregnancy decreases DIO2 production and T3 availability in the placenta. More work is needed to understand how this downregulation affects the maternal delivery of thyroid hormones to the fetus.

Rights Statement

All rights reserved. This copy is provided to the Kenyon Community solely for individual academic use. For any other use, please contact the copyright holder for permission.

Available for download on Saturday, December 31, 2022

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