Growth factors and antral follicular development in domestic ruminants

Growth factors of endocrine and/or paracrine origin play determinant roles in antral follicular development. They modulate survival, proliferation and differentiation of follicular cells, acting in interaction with gonadotropins. It is thought that factors belonging to the families of the insulin-like growth factor (IGF-I and -II), epidermal growth factor (EGF and TGF-alpha) and fibroblast growth factor (FGF) can support growth of small antral follicles by enhancing granulosa cell proliferation. During terminal follicular development, i.e. development of large antral follicles strictly dependent on gonadotropin supply, factors such as IGFs and inhibin potentiate the differentiation-promoting actions of gonadotropins on granulosa and thecal cells, respectively. In addition, binding proteins modulate bioavailability of these growth factors in follicles. In particular, terminal follicular development in domestic ruminants is accompanied by important decreases in intrafollicular concentrations of the IGF-binding proteins IGFBP-2, -4 and -5, due to both a decrease in their synthesis by follicular cells and an increase in their degradation by specific intrafollicular proteinases. As a result, IGF bioavailability increases in large antral follicles, enhancing the amplification of gonadotropin action on follicular cells. In contrast, atresia is characterized by an increase in the expression of IGFBP-2, -4 and -5 mRNAs and a decrease in proteolytic degradation of the corresponding proteins, resulting in an increase in their intrafollicular concentrations and a decrease in IGF bioavailability. All these intrafollicular mechanisms, in addition to the privileged endocrine dialogue that establishes between the dominant follicle(s) and the hypothalamo-pituitary complex, contribute to ensuring its (their) final development and to triggering off atresia of the gonadotropin dependent follicles of the cohort.