Several studies have reported that the highly diffusible gas, nitric oxide (NO), is synthesized by rat, mouse and human ovarian cells. Inhibition of NO synthesis lowers the number of ovulated oocytes suggesting that ovarian NO plays a role in ovulation (1-4). We have demonstrated that the rodent ovary expresses endothelial nitric oxide synthase (eNOS) in theca and granulosa cell layers and on the surface of the rat oocyte (Appendix 1). Oocytes obtained from rats treated with NOS inhibitors show a significant alteration in oocyte maturation with a lower percentage of mature oocytes in Metaphase II and a greater percentage of atypical oocytes (Appendix 2). Recently, using mice in which the gene for eNOS has been deleted (eNOS- KO), we have confirmed that murine ovarian oocytes also express eNOS protein. In addition, ovarian weight, ovulation rate and quality of ovulated oocytes were significantly reduced in eNOS-KO mice relative to control wildtype mice. Our results demons chat ovarian NO is necessary for optimum ovulation and show that it plays a role in maturation of mammalian oocytes. The evidence implicating cAMP, cGMP and cAMP-PDE in meiotic maturation, combined with the effect of NO on oocyte maturation, raises the possibility that NO regulates oocyte cAMP level either by increasing cGMP synthesis and/or by stimulating cAMP PDE activity. We hypothesize that oocyte NO production plays an important role in oocyte meiotic maturation, ovulation and early embryonic development. When oocyte eNOS lacking as in eNOS-KO mice, oocyte maturation and ovulation are impaired.
