Introduction: Premature ovarian failure (POF) is a condition that affects ~1% of women and is idiopathic in 7490% of cases. Our mouse model of POF, the Double Mutant (DM), results from oocyte-specific ablation of core 1-derivedO-glycans and complex and hybrid N-glycans. DM females are subfertile at 6-weeks of age and infertile at 9-weeks of age. By 3 months, DM females exhibit POF with ovaries containing fewer developing follicles but more primary 3a follicles. We investigated if 3a follicle development was blocked by assessing if germ cells retained the potential to develop when combined with wildtype somatic cells.
Methods: This study was approved by the Local Ethical Review Panel (University of Oxford). Production of a reaggregated ovary (RO) involves separation and isolation of germ and somatic cells and then combining the two cell types to form a pellet. ROs were generated using germ or somatic cells from Control (Mgat1FFC1galt1FF) or DM (Mgat1FFC1galt1FF:ZP3Cre) mice at 9-weeks and cells from newborn wildtype mice. ROs were transplanted for 21 days beneath the kidney capsule of an ovariectomised immunocompromised mouse.
Results and discussion: Control-germ-ROs contained follicles at the primary and antral stages of development, and DM-germ-ROs contained follicles at all stages of development indicating the arrest of follicle development was overcome (Controls n=6, DM n=6). Control-somatic-ROs contained follicles at all stages of development however the number of primary follicles was increased in DM-somatic-ROs (Controls n=3, DM n=3). Our results suggest that germ cells from DM infertile ovaries retain the potential to develop follicles and this technique provides a potential treatment for POF. Furthermore, our results indicate that DM oocytes are affecting somatic cell physiology, imprinting the POF phenotype and therefore the ability of ovarian somatic cells to sustain follicle development.
This study was funded by a MRC New Investigator grant to SW.
11 Jul 2016 - 11 Jul 2016