Mouse oocytes regulate hyaluronic acid synthesis and mucification by FSH-stimulated cumulus cells

Mucification (or expansion) of the cumulus cells surrounding the oocyte is thought to depend on the direct action of gonadotropins in stimulating production and deposition of hyaluronic acid (HA) in the extracellular matrix. We now report that the oocyte is essential for this process. Either follicle-stimulating hormone (FSH) at 1 micrograms/ml or dibutyryl cAMP at 2 mM induces mucification of intact cumulus cell-oocyte complexes (COCs) in vitro, but fails to stimulate mucification of isolated cumulus cells. HA synthesis by FSH-stimulated cumulus cells is only approximately 3.5% of the value achieved by FSH-stimulated COCs. Isolated oocytes cultured with or without FSH do not synthesize detectable amounts of HA but induce isolated cumulus cells to increase HA synthesis approximately 13-fold in cocultures with FSH. Medium conditioned by isolated oocytes for 5 hr induces nearly the same level of HA synthesis by cumulus cells under the same culture conditions. FSH also stimulates cumulus cells to increase synthesis of dermatan sulfate proteoglycans (DS-PGs) approximately 3-fold, but this stimulation does not depend upon the presence of oocytes. The results indicate that oocytes produce a soluble factor(s) essential in combination with FSH to stimulate HA, but not DS-PG, synthesis by cumulus cells in vitro and that this factor(s) acts independently or downstream from the FSH-induced formation of cAMP.