The DAZ (Deleted in Azoospermia) gene is located on the human Y chromosome and is associated with male infertility in humans. An autosomal form of this gene (DAZ-like (Dazl)) is present in all mammals and is expressed in germ cells, the Dazl itself being an RNA binding protein. Transgenic homozygous Dazl knockout (KO) male and female mice are infertile due to loss of almost all germ cells in early neonatal life. However, in heterozygous (het) females there is a significant increase in ovulation rate and litter size in comparison to their homozygous wild type (wt) littermates, in spite of lower levels of plasma Follicle Stimulating Hormone (FSH), suggesting an alteration in follicle senstiviity to FSH. The aims of this study were to assess follicle numbers in ovaries and follicle FSH-sensitivity in het mice compared to wt mice. The present studies suggest that, although Dazl is an oocyte-specific gene, the putative protein(s) that Dazl affects through RNA binding in the oocyte targets granulosa cells. The influence of Dazl on follicle development occurs through the single copy of Dazl enhancing FSH sensitivity, but the exact mechanism of Dazl on the granulosa cells is unknown. The studies presented in this thesis suggest that follicles from the Dazl het mice have accelerated growth because of a reduced threshold for FSH that allows them to remain for a longer duration within the critical FSH threshold for follicle growth. In addition, this study suggests that the percentage of healthy and atretic follicles in the Dazl wt and het mice is similar in untreated and oFF-treated mice, but that after FSH treatment there are more healthy follicles in het mice. It could be concluded that, in the adult after follicle activation and recruitment into the pool of growing follicles, a single copy of Dazl results in maintained follicle growth, because of increased FSH-sensitivity. Thus, more larger follicles achieve dominance and these subsequently ovulate, leading to an increased litter size.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:663526 |
| Date | January 2007 |
| Creators | Watson, Elaine A. |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/25290 |
Page generated in 0.002 seconds