PDE5 modulates oocyte spontaneous maturation via cGMP-cAMP but not cGMP-PKG signaling.

Phosphodiesterase type 5 (PDE5), a cGMP specific, cGMP binding phosphodiesterase, specifically hydrolyzes cGMP to 5'-GMP. Here, we examine the distribution of PDE5 in mouse ovary and its effects on spontaneous maturation of mouse oocytes. PDE5 is present in oocytes and cumulus cells of big, antral follicles. Inhibition of activity of PDE5 significantly and reversibly inhibits spontaneous maturation of cumulus-oocyte complexes (COCs). Suppressive effect of PDE5 on spontaneous maturation of COCs is not blocked by the inhibitor of cGMP-dependent protein kinase (PKG). While Sildenafil, an inhibitor of PDE5, has a poor effect on cGMP levels, it significantly increases cAMP levels. These results suggest that the activity of PDE5 plays a role in regulating spontaneous maturation of mouse oocytes and imply that an interaction between cGMP and cAMP signal is involved in this process.