Introduction: Premature ovarian failure (POF) is a reproductive disorder which causes defects within the ovaries, normally leading to infertility. The disorder affects 1% of women under the age of 40 with 75% of cases with no known cause, indicating the need for more research. The Double Mutant (DM) mouse model with oocyte-specific deletion of C1galt1 and Mgat1 exhibit follicular POF at 3 months of age. Therefore, this study aimed to investigate the effect of ovarian dysfunction on the primordial follicle pool of one year-old DM and Contol mice.
Methods: This study was approved by the Local Ethical Review Panel (University of Oxford). Deletion of these genes occurs at the primary stage of follicle development due to deletion of floxed genes by a ZP3Cre transgene. Ovaries from Control and DM mice at 1 year of age were collected, fixed, paraffin embedded and sectioned. Every 10th section was stained with hematoxylin and eosin and the number of primordial follicles quantified. A Mann-Whitney U test was carried out to compare the numbers of primordial follicles in Control and DM ovaries.
Results and Discussion: The quantity of primordial follicles within the DM mouse ovaries was significantly reduced compared to Control mouse ovaries (95.586.06 vs 4.257.18, P<0.05, n=4, Control, n=4 DM). These results reveal that ovarian dysfunction within ovaries with follicular POF modifies primordial follicle development since deletion of the genes occurs after primordial follicle activation, at the primary stage of follicle development. This result reveals the profound effect that normal follicular function has on maintaining the primordial follicle pool and therefore it is possible that all follicular POFs result in afollicular POF due to modified paracrine signalling.
This study was partially funded by Nuffield Department of Obstetrics & Gynaecology.
11 Jul 2016 - 11 Jul 2016