Physiological role of lysophosphatidic acid.

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15370052
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: The University of Tokyo
• Principal Investigator: AOKI Junken The University of Tokyo, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学系研究科, 助教授 (20250219)
• Project Period (FY): 2003 – 2004
• Keywords: lysophosphatidic acid / LPA3 / implantation / knockout mice / prostaglandin

Research Abstract

Every successful pregnancy requires proper embryo implantation. (a process of particular importance) Poor implantation rate is a major problem during infertility treatments using assisted reproductive technologies (ART). We report a new molecular influence on implantation through the lysophosphatidic acid (LPA) receptor LPA_3/edg7. Targeted deletion of LPA_3 resulted in significantly reduced litter size, which could be attributed to delayed implantation and altered embryo spacing. These two events led to embryo death or delayed embryonic development and hypertrophic placentas shared by multiple embryos. An enzyme demonstrated to influence implantation, cyclooxygenase-2 (COX-2), was down-regulated in LPA_3-deficient uteri during preimplantation. COX-2 produces prostaglandins that are critical for implantation ^1, and exogenous administration of the prostaglandins PGE_2 and cPGI into LPA_3-deficient females rescued delayed implantation but did not rescue defects in embryo spacing. These data identify LPA_3 receptor-mediated signaling as a new influence on implantation and further indicate linkage between LPA signalling and prostaglandin biosynthesis.

Research Products

• [Journal Article] LPA3-mediated lysophosphatidic acid signalling in implantation and embryo spacing (2005)
  • Author(s): Xe, Y.et al.
  • Journal Title: Nature 435 Pages: 104-108
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] LPA3-mediated lysophosphatidic acid signalling in implantation.and embryo spacing (2005)
  • Author(s): Tomokazu Amano, Grace Kennedy, Hiroyuki Arai, Junken Aoki, Jerald Chun
  • Journal Title: Nature 435 Pages: 104-108
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1 (2004)
  • Author(s): Hama, K. et al.
  • Journal Title: J.Biol.Chem. 279 Pages: 17634-17639
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identifying Specific Conformations by Using a Carbohydrate Scaffold : Discovery of Subtype-Selective LPA-Receptor Agonists and an Antagonist (2004)
  • Author(s): Tamaruya, Y. et al.
  • Journal Title: Angew.Chem.Int.Ed.Engl 43 Pages: 2834-2837
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mechanisms of lysophosphatidic acid production (2004)
  • Author(s): Aoki, J.
  • Journal Title: Semin.Cell Dev.Biol. 15 Pages: 477-489
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Type II platelet-activating factor-acetylhydrolase is essential for epithelial morphogenesis in C.elegans (2004)
  • Author(s): Inoue, T. et al.
  • Journal Title: Proc.Natl.Acad.Sci. 101 Pages: 13233-13238
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Prostatic acid phosphatase degrades lysophosphatidic acid in seminal plasma (2004)
  • Author(s): Tanaka, M. et al.
  • Journal Title: FEBS Lett 571 Pages: 197-204
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Type II platelet-activating factor-acetylhydrolase is essential for epithelial morphogenesis in C.elegans (2004)
  • Author(s): Takao Inoue, Asako Sugimoto, Yuka Suzuki, Masayuki Yamamoto, Masafumi Tsujimoto, Junken Aoki, Hiroyuki Arai
  • Journal Title: Proc.Natl.Acad.Sci. 101 Pages: 13233-13238
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mechanisms of lysophosphatidic acid production (review). (2004)
  • Author(s): Junken Aoki
  • Journal Title: Semin.Cell Dev.Biol. 15 Pages: 477-489
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prostatic acid Phosphatase Degrades Lysophosphatidic Acid in Seminal Plasma (2004)
  • Author(s): Masayuki Tanaka, Yasuhiro Kishi, Yasukazu Takanezawa, Yoshiyuki Kakehi, Junken Aoki, Hiroyuki Arai
  • Journal Title: FEBS Lett. 571 Pages: 197-204
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identifying Specific Conformations by Using a Carbohydrate Scaffold : Discovery of Subtype-Selective LPA-Receptor Agonists and an Antagonist. (2004)
  • Author(s): Tamaruya Y, Suzuki M, Kamura G, Kanai M, Hama K, Shimizu K, Aoki J, Arai H, Shibasaki M.
  • Journal Title: Angew.Chem.Int.Ed.Engl. 43 Pages: 2834-2837
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1. (2004)
  • Author(s): Hama K, Aoki J, Fukaya M, Kishi Y, Sakai T, Suzuki R, Ohta H, Yamori T, Watanabe M, Chun J, Arai H.
  • Journal Title: J.Biol.Chem. 279 Pages: 17634-17639
  • Description: 「研究成果報告書概要(欧文)」より