The role of PDE5a in oocyte maturation of zebrafish

The importance of cyclic guanosine monophosphate (cGMP) signaling pathway in oocyte maturation has recently attracted much attention in vertebrates. Previously, using zebrafish as a model, we have revealed the role of cGMP and the action of cGMP protein kinase (PKG) in oocyte maturation. In the present study, the function of a cGMP specific phosphodiesterase (PDE5a) is further analyzed in oocyte maturation in zebrafish. Two distinct PDE5a coding genes (named PDE5aa and PDE5ab) were identified in zebrafish, and expressed in most adult tissues including ovary. Both pde5aa and pde5ab mRNA are predominantly expressed in the oocyte but not in follicular cells. Two commercial antibodies targeted to mammalian PDE5a and phosphorylated PDE5a were validated in zebrafish, and we found both antibodies can be used to detect PDE5ab and phosphorylated PDE5ab of zebrafish, respectively. Using both antibodies, we found PDE5ab is only expressed in the oocyte and the phosphorylation of PDE5ab in oocyte could be activated during oocyte maturation induced by human chronic gonadotropin. Intriguingly, we found that the oocyte maturation could be stimulated by treatment of either two different PDE5a inhibitors, sildenafil or tadalafil, and such effects could be completely blocked by a PKG inhibitor KT5823 and two gap junction blockers, respectively. All of these results clearly demonstrate the importance of PDE5a in maintaining the oocyte maturation of zebrafish. When compared with mammals, the functional model of PDE5a is different in zebrafish, suggesting the function of PDE5a might shift from the oocyte in fish to the granulosa cell in mammals during evolution.