NITRIC-OXIDE AS A REGULATOR OF EMBRYONIC-DEVELOPMENT

The role of nitric oxide (NO) in activation of cGMP is well establishe d It has been proposed that the ratio of cAMP to cGMP may be important in the regulation of preimplantation embryonic growth and differentia tion. Therefore, we determined the ability of murine preimplantation e mbryos to produce NO. In addition, NO as an endogenous smooth muscle r elaxant and vasodilator is a candidate for involvement in embryo impla ntation because this process requires increased vascular permeability and uterine quiescence at the sites of blastocyst apposition. Nitrite assays, an indirect measure of NO production, indicate that preimplant ation murine embryos produce NO. This production was reversibly inhibi ted by culture of embryos in medium containing a nonspecific NO syntha se (NOS) inhibitor (N-G-nitro-L-arginine). Additionally, inhibition of normal development was observed in embryos cultured with NOS inhibito r. NO levels increased in culture medium when ovariectomized progester one-treated animals were exposed to estrogen for 1 h in utero. Such ho rmonal treatment induces implantation. These data indicate that NO lev els are regulated by estrogen and may be important in regulation of im plantation. In addition, these data demonstrate for the first time tha t NO production appears to be required for normal embryonic developmen t.