Date of Award

5-2025

Degree Type

Honors College Thesis

Academic Program

Biological Sciences BS

Department

Biological Sciences

First Advisor

Yanlin Guo, Ph.D.

Advisor Department

Biological Sciences

Abstract

The blastocyst faces significant immunological challenges during implantation, including heightened inflammation, which can contribute to implantation failure. Trophoblast stem cells (TSCs) and their differentiated forms (TSC-TBs), derived from the trophectoderm (TE) of the blastocyst, play a crucial role in immune modulation. Previous studies suggest that interferon-stimulated genes (ISGs) derived from TSC and TSC-TB provide antiviral protection to embryonic stem cells (ESCs). These findings show indication of a potential antiviral role for placental progenitors in shielding the blastocyst. Additionally, TSCs and TSC-TBs exhibit selectively attenuated immune responses to the proinflammatory cytokine interferon-gamma (IFN-γ) compared to mouse embryonic fibroblasts (MEFs). The attenuated immune responses are likely to prevent cytotoxicity and inflammation that could compromise implantation. However, a comprehensive analysis of IFN-γ stimulated ISG expression in these cells remains limited. Through bioinformatic analysis of RNA-seq datasets, this thesis reveals that TSCs and TSC-TBs exhibit a selective and attenuated response to IFN-γ, characterized by reduced expression of IFN-γ receptors—likely limiting signal transduction and downstream activation of key transcription factors. The analysis of ISGs involved in cell cycle, cell growth, apoptosis, and stress response provide further evidence of the reduced TSCs and TSC-TBs responsiveness to IFN-γ. However, despite the overall dampened response, a subset of immune-associated ISGs remains modestly upregulated following IFN-γ exposure, prompting speculation that these low expression levels might hold physiological significance in providing immune protection to the blastocyst.

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