Blashkiv T. Regulation of Reproductive Function: Role of Nitric Oxide in Ovulation and Implantation Maintenance

An important scientific problem of assessing the role of nitric oxide in the regulation of reproductive function has been solved in this dissertation. Nitric oxide ensures ovulation and implantation. Nowadays it is a fundamental aspect of the physiology of the female reproductive system. It has been established that ovarian NOS is required to ensure the ovulation process, while the lack of NO in the pre ovulation period leads to an increase in fetal death. The preimplantation embryos are sensitive to changes of the NO-level, while the induced change of the NO-level affects implantation and subsequent (postimplantation) embryonic development. The NO-effect influences the quantity of mice's ovarian oocytes at different stages of the estrous cycle. The NOS activity and NO availability is a necessary condition for meiotic maturation of the oocytes; the role of iNOS increases with the development of the follicle and oocyte. Excess of NO might be a factor of the meiosis inhibition at the time of its recovery; as estradiol such prostaglandin E2 and F2 are involved in the regulation of nitric oxide recovery of meiotic oocytes. NO increases a number of cumulus cells with electronegative nuclei. These data on the amplitude of myometrial contractions in experimental conditions give reasons to believe that the functional state of the myometrium at the time of implantation depends on the functioning of mitochondrial aspartate transporter; the mitochondrial carrier itself does not depend on the input of calcium ions through the Ca-uniporters and is NO-dependent; the carrier operates depending on the mitochondrial membrane potential and non-specific conductance of mitochondria. The new data confirms participation of NO/NOS system in the mechanisms of anti-ovarian antibodies influence on the process of meiotic maturation of mice's oocytes. The results prove the participation of nitric oxide in the regulation of reproductive function, namely providing the contractile activity of the myometrium of the uterus during the immune status changes. Contractile activity of the myometrium in experimental immune ovarian failure and a simultaneous blocking it by the nonspecific NO-synthase, and specific blocking of inducible NO-synthase and arginase brings to changes in the myometrium contractile activity of intact animals. Thus, the data confirm the thesis that during implantation, due to changes in mitochondrial arginase activity and by regulating the total production of nitric oxide, mitochondria may be involved in changes of the contractile activity of the myometrium. Keywords: nitric oxide, ovulation, implantation, experimental immune failure of the ovaries, oocytes, oviduct, myometrium, embryos, mitochondria, mitochondrial carriers.