Thesis
Analysis of genes regulating spermatogonial stem cell and mitochondrial function following ethanol exposure
Washington State University
Master of Science (MS), Washington State University
2014
Handle:
https://hdl.handle.net/2376/102945
Abstract
Alcohol exposure causes many adverse effects on body tissues. Spermatogonial stem cells (SSCs) are responsible for sperm production and can be targeted by toxins, such as ethanol. At a cellular level, ethanol interferes with many processes and damages organelles. One damaged organelle, mitochondria, is characterized as being swollen in size, containing reduced/deformed cristae, producing an increased amount of reactive oxygen species and having changes in enzymatic processes. Any damage to the SSCs, to supporting cells and organelles causes issues with male fertility. We have demonstrated previously that ethanol has a significant long term effect on sperm production through the use of SSC transplantation. Results from this study indicate that colonization and spermatozoa production was reduced when ethanol treated mice SSCs were injected into recipients. Further, gene analysis provided evidence that specific SSC genes were also affected in the ethanol treated mice. Although evidence of decreased sperm production in ethanol treated mice was present, the pathway by which this action works and the organelles involved, is still unclear and under current investigation. Further, literature suggests mitochondria play an important role in stem cell (SC) biology by regulating SC vi fate through the control of the energetic balance necessary for SC proliferation and differentiation; however it is unclear of their importance in the testis. We hypothesize that ethanol damages SSC mitochondria, causing a disruption in the self-renewal and differentiation of SSCs. The hypothesis was tested using utilizing transmission electron microscopy to evaluate mitochondrial morphology, SSC functional transplantation assay following ethanol treatment of donor mice, apoptosis analysis and quantitative RT-PCR to understand the impact of ethanol on mitochondrial genes associated with survival, apoptosis and oxidative phosphorylation pathways. Results from this study provide evidence for an intricate network of apoptotic genes regulating stem cell fate after an acute dose of ethanol. Although there was no direct evidence that the significant increase in apoptosis observed in treated animals was due in response of mitochondria from ethanol, future studies should further investigate the role of this organelle for its importance in stem cell biology and energy production necessary for stem cell homeostasis.
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Details
- Title
- Analysis of genes regulating spermatogonial stem cell and mitochondrial function following ethanol exposure
- Creators
- Meghan C. Munter
- Contributors
- James K. Pru (Degree Supervisor)
- Awarding Institution
- Washington State University
- Academic Unit
- Animal Sciences, Department of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University; [Pullman, Washington] :
- Identifiers
- 99900525063101842
- Language
- English
- Resource Type
- Thesis