Bone morphogenetic protein 4 (BMP-4) and BMP-7 induce vascular endothelial growth factor expression in bovine granulosa cells

Bone morphogenetic protein-4 (BMP-4) and BMP-7, theca cell-derived growth factors, directly affect the granulosa cell function. The aim of this study was to examine the involvement of BMP-4 or BMP-7 in vascular endothelial growth factor (VEGF) expression in bovine granulosa cells. Granulosa cells were collected from small follicles (46 mm) and seeded at a density of 25 X 105 cells per well in Dulbecco's modified Eagle's medium (DMEM)/F12 medium with BMP-4 or BMP-7. The expression of VEGF messenger RNA and protein was the maximum when 1.0 ng/mL of BMP-4 was added to the culture medium. On the other hand, 10 ng/mL of BMP-7 significantly increased the expression of the VEGF gene and protein. In addition, BMP-4 stimulated the expression of Smad1 and Smad5 genes in granulosa cells, whereas BMP-7 stimulated the expression of Smad5 gene. These results suggested that BMP-4 and BMP-7 may be associated with VEGF expression via several specific Smads in bovine granulosa cells: BMP-4 via Smad1/Smad5 and BMP-7 via Smad5. In conclusion, theca cell-derived BMP-4 and BMP-7 might contribute to follicular vasculature and development by inducing VEGF expression in granulosa cells.