Effects of epidermal growth factor on the growth and differentiation of cultured mouse ovarian follicles.

The aim of this investigation was to determine the influence of epidermal growth factor (EGF) on follicular growth and steroidogenesis in mice. Follicles were cultured in medium containing human recombinant EGF at concentrations of 1-20 ng ml-1. Oestradiol production was assayed immunoenzymatically, and growth was measured by recording follicle diameter daily and by analysing the total DNA content of follicles. The effect of EGF on cumulus-oocyte complexes isolated from cultured follicles was also assessed. Results showed that EGF inhibited oestradiol production in a dose-dependent manner, but had no mitogenic effect. Despite almost complete inhibition of oestradiol production at concentrations of EGF > or = 10 ng ml-1, follicles were still able to achieve preovulatory size and morphology, although the incidence of atresia was increased over controls. Conversely, at a concentration of only 1 ng EGF ml-1, a significantly greater number of follicles reached the Graafian stage compared with control follicles. Cumulus expansion and meiotic maturation by isolated cumulus-oocyte complexes from cultured follicles was dramatically stimulated in the presence of EGF and FSH, but not by FSH alone. These findings suggest that EGF may have a modulatory effect on oestradiol production in vivo, and that follicular growth and differentiation may be uncoupled from steroidogenesis. Finally, ovulatory changes in the cumulus-oocyte complex may require the presence of this factor.