Evidence for a functional bone morphogenetic protein (BMP) system in the porcine ovary.

Bone morphogenetic proteins (BMPs) play important roles in controlling fertility and ovulation rate. There is however, little information on the BMP system in the ovary of a large polyovular species. The aims of the present study were to investigate BMP-2 and -6 protein expression in the porcine ovary, their effects on granulosa cells in culture and their mechanism of action. Cells and oocytes were recovered from healthy antral follicles 2-6mm in diameter. When assessed by Western blotting, oocytes and follicular fluid contained BMP-2 and -6. In addition, BMP-2 and -6 were observed in granulosa cells and BMP-2 was also found in theca cells. Granulosa cells were cultured in a serum-free system for 144 h in the presence of increasing doses (0, 3, 30 and 100 ng/ml) of BMP-2 or BMP-6. Both BMPs suppressed progesterone production in a dose-dependent manner after 48 h (P<0.001) and 144 h (P<0.05). Only BMP-6 stimulated cell proliferation at 100 ng/ml (P<0.05). Investigation into the mechanism of action found that BMP-2 and -6 decreased cyclic adenosine monophosphate (cAMP) production (P<0.01), expression of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) protein (P<0.001) and steroidogenic acute regulatory protein (StAR) (BMP-6 only; P<0.05). This supports the hypothesis that BMP-2 and -6 act as luteinization inhibitors. In conclusion, these findings provide evidence for the presence of a complex signalling mechanism in the porcine ovary and suggest that both BMP-2 and -6 may act in a paracrine manner to control granulosa cell function in this large polyovulatory species.