Abortive expansion of the cumulus and impaired fertility in mice lacking the prostaglandin E receptor subtype EP <sub>2</sub>

  • Hiroko Hizaki
    Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, and Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu 520-21, Japan; and Division of Molecular and Cellular Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka 594-1101, Japan
  • Eri Segi
    Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, and Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu 520-21, Japan; and Division of Molecular and Cellular Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka 594-1101, Japan
  • Yukihiko Sugimoto
    Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, and Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu 520-21, Japan; and Division of Molecular and Cellular Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka 594-1101, Japan
  • Masaya Hirose
    Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, and Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu 520-21, Japan; and Division of Molecular and Cellular Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka 594-1101, Japan
  • Tomomi Saji
    Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, and Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu 520-21, Japan; and Division of Molecular and Cellular Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka 594-1101, Japan
  • Fumitaka Ushikubi
    Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, and Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu 520-21, Japan; and Division of Molecular and Cellular Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka 594-1101, Japan
  • Toshiyuki Matsuoka
    Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, and Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu 520-21, Japan; and Division of Molecular and Cellular Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka 594-1101, Japan
  • Yoichi Noda
    Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, and Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu 520-21, Japan; and Division of Molecular and Cellular Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka 594-1101, Japan
  • Takashi Tanaka
    Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, and Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu 520-21, Japan; and Division of Molecular and Cellular Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka 594-1101, Japan
  • Nobuaki Yoshida
    Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, and Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu 520-21, Japan; and Division of Molecular and Cellular Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka 594-1101, Japan
  • Shuh Narumiya
    Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, and Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu 520-21, Japan; and Division of Molecular and Cellular Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka 594-1101, Japan
  • Atsushi Ichikawa
    Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, and Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu 520-21, Japan; and Division of Molecular and Cellular Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka 594-1101, Japan

抄録

<jats:p> Female mice lacking the gene encoding the prostaglandin (PG) E <jats:sub>2</jats:sub> receptor subtype EP <jats:sub>2</jats:sub> (EP <jats:sub>2</jats:sub> <jats:sup>−/−</jats:sup> ) become pregnant and deliver their pups at term, but with a much reduced litter size. A decrease in ovulation number and a much reduced fertilization rate were observed in EP <jats:sub>2</jats:sub> <jats:sup>−/−</jats:sup> females without difference of the uterus to support implantation of wild-type embryos. Treatment with gonadotropins induced EP <jats:sub>2</jats:sub> mRNA expression in the cumulus cells of ovarian follicles of wild-type mice. The immature cumuli oophori from wild-type mice expanded <jats:italic>in vitro</jats:italic> in response to both follicle-stimulating hormone and PGE <jats:sub>2</jats:sub> , but the response to PGE <jats:sub>2</jats:sub> was absent in those from EP <jats:sub>2</jats:sub> <jats:sup>−/−</jats:sup> mice. Cumulus expansion proceeded normally in preovulatory follicles but became abortive in a number of ovulated complexes in EP <jats:sub>2</jats:sub> <jats:sup>−/−</jats:sup> mice, indicating that EP <jats:sub>2</jats:sub> is involved in cumulus expansion in the oviduct <jats:italic>in vivo</jats:italic> . No difference in the fertilization rate between wild-type and EP <jats:sub>2</jats:sub> <jats:sup>−/−</jats:sup> mice was found in <jats:italic>in vitro</jats:italic> studies using cumulus-free oocytes. These results indicate that PGE <jats:sub>2</jats:sub> cooperates with gonadotropin to complete cumulus expansion for successful fertilization. </jats:p>

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