Mouse Embryonic Stem Cells Are Sensitive to the Cytotoxicity of Nitric Oxide: Biological Implications for Early Embryogenesis
Date of Award
Honors College Thesis
Yan-Lin Guo, Ph.D
The early embryo, before implantation, is at a very vulnerable stage in development where it faces various inflammatory cytokines throughout the implantation process. In this stage, the cells in the blastocyst, the preimplantation stage embryo, must proliferate rapidly for tissue formation. However, it is known that inflammatory cytokines can inhibit cell proliferation. Previous studies have shown that embryonic stem cells (mESCs), the major cell component in the blastocyst, are unresponsive to treatments of tumor necrosis factor ⍺ (TNF⍺) and interferon 𝛾 (IFN𝛾), two inflammatory cytokines involved in the implantation process. Treatment of mESC-differentiated fibroblasts (mESC-FBs) with TNF⍺ and IFN𝛾 in combination (TNFα/IFNγ) significantly reduced cell viability and the rate of cell proliferation; however, this treatment has no effect on the cell viability and the cell cycle of mESCs. It has been previously demonstrated that inducible nitric oxide synthase (iNOS) stimulated by TNFα/IFNγ is responsible for the effects of TNFα/IFNγ, since NO produced by iNOS is a free radical that can cause cellular damage. Based on this finding, it is hypothesized that the resistance of mESC to TNFα/IFNγ cytotoxicity is due to their lack of response to these two cytokines, therefore, iNOS and NO were not produced. This allows mESCs to avoid the cytotoxicity of TNFα/IFNγ. To test this hypothesis, sodium nitroprusside (SNP), a NO donor, was used to determine the sensitivity of mESCs to NO. SNP treatment resulted in decreased cell viability through increasing apoptosis, suggesting that mESCs are susceptible to the cytotoxicity caused by NO. Therefore, the lack of iNOS induction by TNFα/IFNγ in mESCs may help to protect mESCs from the cytotoxicity of the two cytokines at the early stage of embryogenesis.
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Hargis, McKenzie C., "Mouse Embryonic Stem Cells Are Sensitive to the Cytotoxicity of Nitric Oxide: Biological Implications for Early Embryogenesis" (2020). Honors Theses. 724.