Inhibition of oocyte maturation by nitric oxide synthase 1 (NOS1) in zebrafish

It is well-documented that nitric oxide (NO) is an important regulator of oocyte maturation in mammals. Conversely, the function of NO during oocyte maturation has received little attention in nonmammalian vertebrates. NO is produced from L-arginine through the action of the enzyme NO synthase (NOS). Herein, we examined the expression, hormonal regulation, and involvement of NOS in meiotic signaling in zebrafish oocyte maturation. Three types of nos genes, nos1, nos2a, and nos2b, have been identified in zebrafish. We found that the expression of nos1 was highest in the ovary among the three nos genes, with maximal expression in full-grown (FG)-stage follicles during folliculogenesis. In addition, the concentration of NO was reduced during oocyte maturation and this corresponded with the decreased expression of nos1 in the follicular cell layers, suggesting that NOS1-derived NO may be one of the inhibitors of oocyte maturation in zebrafish. This is the first description of nos1 involvement in oocyte maturation in vertebrates. Moreover, the NO donor SNAP (S-nitroso-l-acetyl penicillamine) partially attenuates human chorionic gonadotropin (hCG)- and 17,20β-P-induced GVBD (germinal vesicle breakdown), perhaps by increasing cGMP levels during oocyte maturation. Finally, our results showed that SNAP and the cGMP analog 8-Br-cGMP inhibited hCG-induced mitogen-activated protein kinase (MAPK) activation, further indicating that NO and cGMP block oocyte maturation in zebrafish.