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

ABSTRACT 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 (4–6 mm) and seeded at a density of 2–5 × 10 5 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.