Introduction: The regulation of follicle development is not well understood, despite its importance in determining fertility, but there is evidence that the oocyte plays a key role. The female C1galt1 Mutant mouse has an oocyte-specific deletion of the T-synthase enzyme and as a result cannot synthesise core 1-derived O-glycans. Mutant females exhibit a phenotype of increased fertility and altered follicle development. To investigate the hypothesis that changes in the development of Mutant follicles would manifest as differences in follicle morphology during development, a histological assessment of ovaries from 3-week-old Control and Mutant mice was carried out.
Methods: This study was approved by the Local Ethical Review Panel (University of Oxford). Ovaries were collected from 3-week-old Control and Mutant mice. Ovaries were fixed, embedded, sectioned and every tenth section stained with haematoxylin and imaged. Healthy follicles with a visible nucleus were analysed using ImageJ software. Follicle stage was determined by the number of layers of granulosa cells and antrum area.
Results and discussion: Analysis of follicle counts confirmed that there are more healthy follicles in Mutant ovaries compared to Control ovaries (P<0.001) (n=4 Control, n=4 Mutant). Oocyte diameter and theca area were the same in Control and Mutant follicles of comparable development. However, Mutant follicles with the same number of granulosa cells as Control follicles have a smaller antrum (P<0.05) (n=29 Control, n=48 Mutant). Therefore, follicle morphology is altered in the Mutant during follicle development. These changes are consistent with the previously proposed model that follicle development is delayed in the Mutant compared to Control mice. Furthermore, it is evidence that one or more oocyte-derived proteins possessing core 1-derived O-glycans has a function in regulating the formation of the antrum. This study was partially funded by Nuffield Department of Obstetrics and Gynaecology.
11 Jul 2016 - 11 Jul 2016