Theses and Dissertations from UMD

Permanent URI for this communityhttp://hdl.handle.net/1903/2

New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM

More information is available at Theses and Dissertations at University of Maryland Libraries.

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    Novel Models for Studying Trophoblast Development and Placental Pathologies
    (2019) Pence, Laramie; Telugu, Bhanu; Molecular and Cell Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Placental development begins in the mammalian blastocyst, when the first lineage specification event commits one cell population to making extraembryonic tissues, including the placenta, and commits another cell population to making the embryo proper. The mouse is an excellent animal model to study these early events and how the resulting placenta organ supports normal fetal development and a healthy pregnancy in the mother. The studies included in this Dissertation use the mouse to understand the role of long non-coding RNAs during early placental development, and to create a lineage biasing model that takes advantage of what is known about the first lineage specification event in mammals. Using expression analysis and the CRISPR/Cas9 system to create a knockout mouse strain, a placental-specific lncRNA was discovered and shown to be expressed in derivatives of the ectoplacental cone. Additionally, using the line age bias model to cause biased ablation of Hif1α in the placenta has revealed a role for fetal vs. placental contribution of resulting phenotypes.
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    A TISSUE-ENGINEERED PLACENTAL BARRIER MODEL FOR TOXICOLOGY AND PHARMACOLOGY APPLICATIONS
    (2019) Arumugasaamy, Navein; Fisher, John P; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Throughout history, there have been two major instances where a substance caused thousands of birth defects, yet it took a few years for the causation to be noted: thalidomide, in the late 1950s and early 1960s, and Zika Virus, just recently in 2014 to 2016. In both instances, the developing fetus was indirectly exposed to the substance through the placental barrier. Pregnant women took thalidomide as a medication or were stung by mosquitos and exposed to Zika Virus. These examples clearly show why models of the placental barrier and downstream fetal tissues are critically needed. Herein, I present our work on the development and utilization of a biomimetic placenta-fetus model. The three objectives in this work were to: (1) develop and validate the tissue-engineered BPB model through study of biologically relevant substances; (2) assess the effects of SSRIs on the BPB’s cells and evaluate the drugs’ transport profile across the barrier; and, (3) assess how SSRIs influence cardiomyocyte signaling and injury biomarker release following passage through the BPB. We suggest that this work provides a critically needed and biologically relevant placenta-fetus model, useful as a method to assess pharmacology and toxicology properties of medications and other substances. Moreover, the knowledge gained through the studies performed may hopefully improve clinical care of pregnant women through enhanced understanding of how a medication impacts both the pregnant mother-to-be and her developing fetus.