Kit ligand and basic fibroblast growth factor interactions in the induction of ovarian primordial to primary follicle transition.

Ovulated eggs during a female's reproductive life are derived from a pool of primordial follicles arrested in prophase of the first meiotic division. When follicles leave the resting pool they undergo a primordial to primary follicle transition and will grow and develop until either ovulation occurs or follicles undergo atresia. Several growth factors have been implicated as acting locally within the ovary to regulate the primordial to primary follicle transition. How these growth factors may interact and cooperate to perform this vital function remains to be elucidated. The objective of the current study is to investigate interactions between kit ligand (KL) (i.e. stem cell factor) and basic fibroblast growth factor (bFGF) that promote the primordial to primary follicle transition in rat ovaries. Ovaries were removed from 4-day-old rat pups and cultured for 2 weeks with KL alone or with KL and a neutralizing antibody against bFGF. The ability of KL treatment to increase primordial follicle transition was blocked with a bFGF neutralizing antibody. In addition, ovary cultures were treated with bFGF alone or with bFGF and an anti-c-kit receptor antibody which blocks KL signaling. The ability of bFGF treatment to increase primordial follicle transition was blocked with an anti-c-kit receptor antibody. Observations indicate that both KL and bFGF must be active in order to optimally promote the changes that occur in oocytes, granulosa cells, and stromal/interstitial cells when primordial follicles initiate development. Cultured ovaries were treated with either KL or bFGF for 3 days and then bFGF and KL mRNA expression levels in the whole ovary were measured. KL was not found to regulate bFGF expression. In contrast, bFGF treatment was found to increase KL mRNA expression in cultured ovaries. These observations suggest that one function of the oocyte-derived bFGF is to increase the granulosa derived KL expression and that both KL and bFGF are required to optimally promote primordial to primary follicle transition. Elucidating the cell-cell interactions that mediate this network of specific locally derived growth factors is critical to understanding the physiology of the primordial to primary follicle transition.