Figure 8

Model of intact ovarian cord formation and maturation promoting oocyte survival and development in follicles. Prior to ovary development on e13.5, germ cells located in cysts in the e12.5 female genital ridge are not yet competent to survive and form follicles when re-aggregated (re-agg). However, ovary maturation on e13.5 and development of intact ovarian cord structures containing oocyte and somatic granulosa cell clusters are sufficient to permit some oocyte survival and follicle formation upon re-aggregation. By e16.5, intact ovarian cord-enclosed meiotic oocyte clusters and granulosa somatic cells are now primed to undergo robust follicle formation and oocyte development in follicles when re-aggregated. The percentage of surviving re-aggregated oocytes was calculated in comparison to intact transplant controls. Oocyte (green) and granulosa cell (blue) contacts and paracrine signaling factors may promote oocyte survival (+) and possibly facilitate programmed ovarian germ cell cyst break down into follicles. The cord and/or oocyte-mediated recruitment of granulosa cell clusters during ovary differentiation may also provide somatic cell signaling factors such as WNT4, R-spondin1, and Follistatin that promote oocyte survival and maturation. In addition, intact ovarian cords may facilitate the protection of oocytes from re-aggregation induced inhibitory signaling from somatic cells in the genital ridge. Thus, we define a critical window from e13.5 to e16.5 of oocyte enclosure in intact fetal ovarian cord structures for the intrinsic programming of oocytes with competence to survive and undergo further development.