Effect of granulocyte-macrophage colony-stimulating factor deficiency on ovarian follicular cell function

Granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine secre ted by lymphohaemopoietic and other cell lineages, is known to influence ov arian cyclicity and embryo development. The aim of this study was to examin e the effect of GM-CSF on ovarian follicular cell function using GM-CSF-def icient (GM -/-) mice. Immature GM -/- and GM +/+ mice were stimulated with eCG, and cumulus-oocyte complexes and mural granulosa cells were collected 48 h later. Expression of GM-CSF receptor (GM-CSFR) alpha and beta mRNA sub units by cumulus-oocyte complexes and mural granulosa cells was examined us ing RT-PCR. Cumulus-oocyte complexes from both genotypes were found to expr ess mRNA for the GM-CSFR alpha -subunit only, while the mural granulosa cel ls expressed both the alpha and beta receptor subunits. Cumulus-oocyte comp lexes recovered from GM -/- mice had approximately twice the number of cumu lus cells per cumulus-oocyte complex than did those of GM +/+ mice (P < 0.0 5), even though the growth-promoting activity of denuded GM -/- oocytes was found to be equivalent to that of wild-type oocytes. GM-CSF deficiency was associated with marginally increased DNA synthesis in cumulus cells and si gnificantly (P < 0.05) lower progesterone production by mural granulosa cel ls recovered from GM -/- compared with those recovered from GM +/+ mice. Th e addition of rec-mGM-CSF in vitro did not affect DNA synthesis in either c ell type or progesterone production by mural granulosa cells, irrespective of GM-CSF status. There was no effect of GM-CSF deficiency on the capacity of FSH and insulin-like growth factor I to stimulate DNA synthesis in cumul us-oocyte complexes (approximately 15- and threefold, respectively) and in mural granulosa cells (approximately two- and threefold, respectively). Tak en together, these data show that GM-CSF influences events associated with follicular maturation in mice. The effects of GM-CSF are not exerted direct ly in granulosa or cumulus cells, but appear to be mediated indirectly, per haps through the agency of steroidogenesis-regulating secretions of local m acrophage populations residing in the theca.