- Title
- Understanding the production of poor-quality spermatozoa
- Creator
- Netherton, Jacob
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2021
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- The production of poor quality spermatozoa is a hallmark of male infertility. Commonly, men produce ow numbers of cells that have poor morphology and poor motility. Whilst the use of assisted reproductive technologies can help couples suffering from male factor infertility achieve a pregnancy, there is a decrease in live birth rates and health outcomes for the children conceived using poor-quality spermatozoa. While there is currently some understanding of what causes infertility in men, there is still a large portion that is unknown. Included in this are the molecular mechanisms disrupted during spermatogenesis that leads to the production of a poor quality spermatozoon. The overarching aim of this thesis was provide insight into the differences between good and poor quality sperm cells, and attempt to identify the critical functions that may be perturbed during germ cell development to create an abnormal spermatozoon. Initially a proteomic comparison of good and poor-quality cells was performed. This identified that despite the large differences in the spermatozoa abnormalities observed, there are common protein changes between good and poor-quality populations, and these alterations are maintained between individuals. The poor-quality cells had lower amounts of flagella related proteins and increase in general cytoplasmic proteins. The loss of flagella proteins is a likely explanation of the reduced motility within this population, and the increased cytoplasmic protein components is related to the aberrant retention of cytoplasm in these cells. The identified changes may be usefully as markers of poor quality cells when screening couples for fertility. A common characteristic of poor-quality spermatozoa is a disrupted chromatin status. Often infertile men have higher levels of DNA damage, and they are less resistant to chemical denaturation. Herein, a subcellular fractionation of good and poor quality cells allowed for unbiased comparison of the nuclear component of these populations. Interestingly, this comparison revealed that the poor quality nuclei possessed higher amounts of nucleoplasm related proteins. This retention is suggested to be a contributing factor in the failure of these cells to complete nuclear compaction, leaving them vulnerable to DNA damage. To investigate the process within the testes that are responsible for the production poor-quality spermatozoa, a mouse model was used to produce cells that present with a male infertility phenotype (DNA damage, poor motility and poor morphology). Often cells that possess abnormal cell morphology, also have abnormal nuclear morphology. Observation of the nuclear shaping features of spermatogenesis revealed that there as an increase in acrosome and manchette defects 24 and 48 hours following the application of heat to the testis of mice. Abnormalities in these key organelles subsequently resulted in nuclear abnormalities in these cells. The findings within this thesis have increased our understanding of the mechanisms of poor-sperm production, from the protein components that can be used as markers of sperm quality, and pathways involved in poor cell production in the testis. Further investigation of the mechanisms of poor sperm production will hopefully identify viable targets for treatment in infertile men, and subsequently improve fertility outcomes for couples.
- Subject
- spermatozoa; male intertility; spermatogenesis; DNA; thesis by publication
- Identifier
- http://hdl.handle.net/1959.13/1508648
- Identifier
- uon:56143
- Rights
- Copyright 2021 Jacob Netherton
- Language
- eng
- Full Text
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 7 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 437 KB | Adobe Acrobat PDF | View Details Download |