The pro-mature form of bone morphogenetic protein 15 (BMP15) in oocyte maturation medium improves subsequent bovine embryo development (#12)
Oocyte in vitro maturation (IVM) is a procedure that can eliminate hyperstimulation for infertility treatment. Embryo development rates post-IVM needs to be improved and this can be achieved by adding recombinant BMP15 or GDF9 to IVM. Oocytes possibly secrete BMP15 and GDF9 as a complex of the pro- and mature-domains (pro-mature complex, ~65kDa). The aim of this study was to determine effect of pro-mature complex versus mature BMP15 and mature GDF9 during IVM on bovine embryo development and metabolic activity. Immature COCs were aspirated from follicles and randomly distributed into control medium (TCM199 -/+0.1 IU/ml FSH +3 mg/ml BSA) and treated with 100 ng/ml in-house produced pro-mature complex BMP15, or mature BMP15 or mature GDF9 (both R&D Systems). COCs were matured, inseminated and presumptive zygotes cultured for 8 days to the blastocyst stage and stained for cell number. Metabolic measures of glucose uptake and lactate production from COCs and reduced glutathione and autofluorescence of NAD(P)H and FAD++ were measured in oocytes after IVM. COCs matured in medium -/+FSH containing pro-mature complex BMP15 displayed significantly improved blastocyst development (43.5 ± 4.2%, 57.7±3.9%) compared to controls (28.9±3.7%, 43.3±2.4%, respectively) and to mature GDF9+FSH (36.1±3.0%). The mature form of BMP15 produced intermediate levels of blastocyst development (-/+FSH; 32.3±4.5%, 50.1±2.6%, respectively), which were not significantly different to pro-mature complex BMP15 or controls. Pro-mature complex BMP15 increased intra-oocyte NAD(P)H and reduced glutathione levels were increased by pro-mature complex BMP15 (P=0.058) and mature BMP15 (P<0.05) but not by GDF9. Exogenous BMP15 in its pro-mature complex form during IVM provides a functional source of oocyte-secreted factors to improve bovine blastocyst development, which could be mediated by the provision of a reductive environment in the oocyte. Identification of the form of BMP15 which improves embryo development is a significant step for cattle embryo production and human infertility treatment.