The initiation of follicle growth is defined as the transition of primordial follicles from the quiescent to the growth phase. We have shown that follicle growth initiation consists of two distinct, consecutive phases. The first phase is characterized by the transformation of granulosa cells from flattened to cuboidal in shape and by their proliferation, this coincides with follistatin expression. During the second phase, an increase in the number of granulosa cells is accompanied by an increase in the size of the oocyte. Evidence from other species confirms this observation. It seems that a prerequisite for initiation of oocyte growth is the presence of cuboidal granulosa cells. The vast majority of bovine primordial follicles enter the first phase of growth when cultured in serum-free medium. Similar results have been obtained for human primordial follicles. Two proteins of oocyte origin, GDF9 and BMP15, play an essential role in granulosa cell proliferation beyond the primary stage. It can be speculated that the regulation of follicle growth initiation is a two-phase event: the first phase depends on locally produced inhibitory and stimulatory factor(s); in the second phase the follicle become an autonomous unit, whose further development depends on oocyte-produced GDF9/BMP15 and the kit ligand derived from granulosa cells.
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