The receptor tyrosine kinase Ron is expressed in the mouse ovary and regulates inducible nitric oxide synthase levels and ovulation.

Abstract Objective To determine the reproductive effects in mice of the deletion of the tyrosine kinase domain of the Ron receptor. Design Controlled animal studies. Setting Academic research environment. Animal(s) Immature mice with deletion of the tyrosine kinase domain of the Ron receptor (TK−/−) at 22–30 days of age and adult black Swiss female mice at 5–6 weeks of age. Intervention(s) Hormonal stimulation of immature female TK−/− animals to induce ovulation. Main outcome measure(s) Ovulation rates measured by counting the total number of cumulus oocyte complexes in the ampullar region of the murine oviduct after hormonal stimulation. Western blot analysis measured murine ovarian protein levels of endothelial and inducible nitric oxide synthase (iNOS). Immunohistochemical analysis localized iNOS in the developing murine ovarian follicle. Result Immature TK−/− mice (22–30 days) ovulate significantly fewer cumulus oocyte complexes. Western blot analyses demonstrated increased levels of iNOS before and after ovulation compared with controls. Conversely, endothelial nitric oxide synthase levels were similar and remained constant during corresponding time periods. Immunohistochemical analyses demonstrated a significant increase in iNOS staining throughout the ovary in TK−/− mice with a significant amount of iNOS in granulosa cells surrounding the oocyte when compared with controls. Conclusion(s) The increased level of nitric oxide in the TK−/− mice is likely due to an elevated level of iNOS, which may contribute to a decrease in the size of the ovaries and ovulation rates of immature TK−/− animals.