Growth promoting activity of oocytes on granulosa cells is decreased upon meiotic maturation

An increasing body of evidence indicates that the oocyte plays an active role in the control of ovarian follicle development in mammals. In the present study, we have examined the role of oocytes in regulating granulosa cell proliferation. Rat and bovine oocytes cocultured with rat granulosa cells stimulated granulosa cell DNA synthesis and DNA content in the cultures. FSH or cAMP further amplified this effect. Poor-quality oocytes showed a marked decrease in their stimulatory effect. Stimulation of DNA synthesis by bovine oocytes seems to be cell-type specific, since Swiss 3T3 fibroblasts and CCL-64 mink lung epithelial cells were not responsive, while primary cultures of rat and bovine granulosa cells and the bovine granulosa cell line BGC-1 showed significant responses. Oocyte-conditioned medium produced only a slight stimulation of rat granulosa cell DNA synthesis. However, the effect of oocyte coculture was dependent on the total incubation volume, suggesting that the growth promoting activity was mediated by a soluble factor. The stimulation elicited by bovine oocytes was evident even in the presence of maximally effective doses of transforming growth factor-beta or tumor necrosis factor-alpha, indicating that neither of these growth factors was responsible for this effect. In vitro maturation of bovine oocytes was associated with a marked decrease in the stimulatory activity. This decrease was partially prevented when maturation was blocked by addition of cycloheximide. Comparison of the developmental pattern of the secretion of the growth promoting activity with that of the cumulus expansion-enabling factor indicated that both activities can be dissociated. Our data suggest the existence of a very labile factor produced by the oocyte before completion of the first meiotic division that promotes granulosa cell proliferation.