ABSTRACT

Commencing with follicle formation and continuing throughout folliculogenesis, bi-directional cell-cell interactions between oocytes and their companion granulosa cells are essential for the coordinated development of both the germs cells and the somatic compartments of the follicle. Indeed, it is now well established that oocytes and granulosa cells are dependent on each other for growth and survival throughout the different stages of follicular development as normal oocyte development cannot take place without the supporting somatic cells of the follicle and visa versa37,38. Furthermore, the rate of oocyte growth in vitro appears to be directly correlated to the number of granulosa cells surrounding it39. This is a possible reflection of the amount of uridine, choline, and amino acids incorporated into the oocyte, which also varies with the number of attached supporting cells19,20. However, while it also appears that different types of communication-competent somatic cells can support oocyte survival in vitro, the great majority of evidence indicates that oocytes are dependent on secreted soluble growth factors, meiotic inhibitors, and stimulators from the granulosa cells for their growth and development. For example, Cecconi et al.40 demonstrated that granulosa cell conditioned medium could support limited growth of denuded mouse oocytes cultured on mouse fibroblasts cells. Interestingly, the same authors also detected oocyte growth when Sertoli cell conditioned medium was used, suggesting either that Sertoli cells share a common origin with granulosa cells, or that gonadal somatic cells secrete similar growth factors to support germ cell growth. In contrast, other authors have shown that denuded murine oocytes do not grow if cultured on Sertoli cells, 3T3 cells, primary mouse fibroblast cells, L-cells, Chinese hamster ovarian cells, and mouse hepatoma cells38-40, whereas co-culture with granulosa cells has been

consistently shown to induce phosphorylation of specific proteins in the oocyte41. Furthermore, maximal oocyte growth is obtained when denuded oocytes are in direct contact with granulosa cells42, whereas denuded oocytes co-cultured with, but not in direct contact with, follicle cells had a 60% reduced growth rate compared to their direct contact counterparts.