Bi-directional communication between the oocyte and surrounding cumulus vestment is critical for developmental competence. Cumulus cells are important for providing the oocyte with substrates for energy production, and in turn, oocyte-secreted factors (OSF) such as bone morphogenetic protein 15 (BMP15) regulate cumulus cell function to support oocyte maturation. We hypothesize that the beneficial effects of BMP15 on developmental competence are through regulation of COC metabolism, acting via cumulus cells. The aim of this study was to determine the influence of recombinant human BMP15 (rhBMP15) and FSH (a known stimulator of metabolism) supplementation on the metabolism of bovine cumulus oocyte complexes (COCs).

Bovine COCs were matured in TCM199 + BSA ±FSH ±rhBMP15 for 23h. The addition of FSH and rhBMP15 increased blastocyst development (-FSH –rhBMP15=28.4±7.4% vs. +FSH+rhBMP15=51.5±5.4%; P<0.05). Regardless of rhBMP15, +FSH increased glucose consumption and lactate production >2-fold (main effect, P<0.05). +rhBMP15 resulted in decreased ADP and increased ATP:ADP in COCs, indicative of increased proliferation and cellular activity. There were no significant differences between treatments in ATP, ADP and ATP:ADP in denuded oocytes (DO). Cellular REDOX state and mitochondrial activity (oxidative phosphorylation) were determined by measuring NAD(P)H and FAD⁺⁺ fluorescence. Intra-oocyte FAD⁺⁺ and NAD(P)H intensities were significantly higher in COCs +rhBMP15, whereas the presence of FSH diminished this effect. Furthermore, the stimulatory effect of rhBMP15 was not seen in DOs cultured ±FSH ±rhBMP15. Regardless of treatment, there were no significant differences in intra-oocyte REDOX ratios (FAD⁺⁺:NAD(P)H) of COCs or DOs.

These results suggest that FSH stimulates glycolysis within cumulus cells and rhBMP15 stimulates oxidative phosphorylation within the oocyte, most likely via the cumulus cells.  However, the combination of FSH and rhBMP15 results in equilibrium between these metabolic pathways.