Benefits of 8-bromo-guanosine 3',5'-cyclic monophosphate (8-br-cGMP) in human ovarian cortical tissue culture.

Guanosine 3',5'-cyclic monophosphate (cGMP) is an important intracellular second messenger in many cells of the body; however, its importance in the ovary is only now being realized. The effects of the cGMP analogue 8-bromo-guanosine 3',5'-cyclic monophosphate (8-br-cGMP) were tested on human ovarian follicle development and survival using an established tissue culture method. Ovarian biopsies were collected from 27 women (mean age 32 years) undergoing Caesarean sections or gynaecological operations. Tissue was cut into small pieces and cultured in the presence or absence of 5 mmol/l 8-br-cGMP for 7 and 14 days. 8-br-cGMP enhanced the rate of follicle growth to the secondary stage after both 7 and 14 days of culture. Furthermore, it significantly improved the proportion of viable follicles when compared with control cultures. All cultured follicles reaching the secondary stage were smaller than those uncultured. This suggests that although granulosa cells were stimulated to proliferate and form a double layer, the cells themselves did not become larger as usually occurs with maturation and differentiation. Oestradiol production was greater in the 8-br-cGMP-containing cultures after 12 days compared with control cultures, presumably due to the concurrent increase in the proportion of secondary follicles. In the early stages of human ovarian tissue culture, 8-br-cGMP may be a necessary component as both a growth enhancer and survival factor.