Reproduction Abstracts

Premature ovarian failure (POF) affects around 1% of women and is idiopathic in 74–90% of cases. Our mouse model of POF, the double mutant (DM), are fertile at 6-weeks and undergo POF by 3-months consistent with a decline in developing follicles. However, DM ovaries have increased numbers of primary follicles at the 3a stage, indicating a block in follicle development.

We investigated whether we could rescue the ability of DM oocytes at 3- and 9-weeks to coordinate follicle development by replacing DM somatic cells with WT using the reaggregated ovarian pellet (ROP) technique. Production of a ROP involves separation of the ovary into single cells, isolation of the different cell types, and then combining cells to generate a chimeric ROP. The ROP is transplanted under the kidney capsule of ovariectomised immune-compromised mice to develop for 21 days when antral follicles can be observed.

In ROPs generated using 3-week DM oocytes and WT somatic cells (n=3), follicles were present from the secondary stage onwards suggesting the DM 3a follicle development block was overcome. However, ROPs generated using 3-week control oocytes contained follicles from all stages but in much higher numbers. For ROPs generated using 9-week old control (n=3) or DM oocytes (n=3), although follicle numbers were equivalent between control and DM, follicles in the DM ROP were at more advanced stages of follicle development compared to control.

In summary, oocytes from mice with POF retain the potential to regulate follicle development and thus this technique identifies a potential treatment for POF.