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Study on control mechanism of maintenance of pregnancy and induction of parturition by lysophosphatidic acid

Research Project

Project/Area Number 16K08076
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Integrative animal science
Research InstitutionKitasato University

Principal Investigator

Kurusu Shiro  北里大学, 獣医学部, 教授 (50215076)

Co-Investigator(Kenkyū-buntansha) 汾陽 光盛  岡山理科大学, 獣医学部, 教授 (00153007)
杉山 真言  北里大学, 獣医学部, 助教 (30648225)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords妊娠 / 分娩 / リゾホスファチジン酸 / ラット / 黄体 / 子宮 / オートタキシン / 生体情報 / 脂質メディエーター
Outline of Final Research Achievements

A bolus administration of antibody or chemical inhibitor (S32826) against autotaxin, an LPA-synthesizing enzyme, to mid- and late-pregnant rats resulted in altered progesterone secretion from corpus lutea and altered timing of parturition. The temporal changes are both advanced and delayed with a half- or one day. Local (ovarian bursal) and systemic (iv) injections caused partly different responses, suggesting distinct biological effects of autotaxin-generating LPA between corpus lutea and circulatory system. Local challenge resulted in decreases in steroidogenic cell size and blood flow in luteal tissues. LPA exerted a significant uterotonic effect, which was unlikely mediated by PGF2a synthesis and action. Placental expression of autotaxin and LPA receptors increased toward the end of pregnancy. The main immunoreactive sites were cytosol in decidual and giant cells. Autotaxin and LPA may play diverse roles in maintenance and termination (parturition induction) of pregnancy in rats.

Academic Significance and Societal Importance of the Research Achievements

母体の妊娠、並びに胎仔の発育機構について格好の研究モデルであるラットを用いて、卵巣、子宮、胎盤の複数の臓器においてautotaxinが発現し、おそらくはLPAの合成・作用を介して個々の機能の発現を調節していることを示唆する基礎情報を得た。その機能は、少なくとも卵巣細胞のステロイド分泌とサイズ調節、局所の血流量、子宮の平滑筋収縮と多様である。分娩発来への循環血中ATXの影響は興味深いところである。もとより生殖は動物種差の大きい機構であり、この動物モデルでの知見が産業動物等に外挿されるかは不明であるが、例えばヒトの妊娠高血圧症候群との関連が想定され、トランスレーショナル研究への展開が求められる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (36 results)

All 2018 2017 2016

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (29 results) (of which Int'l Joint Research: 16 results,  Invited: 1 results)

  • [Journal Article] Effects of gonadotropin-releasing hormone agonist on human chorionic gonadotropin activity in granulosa cells of immature female rats.2018

    • Author(s)
      Tungmahasuk D, Fungbun N, Laoharatchatathanin T, Terashima R, Kurusu S, Kawaminami M.
    • Journal Title

      Journal of Veterinary Medical Sciences

      Volume: 64 Pages: 129-134

    • NAID

      130006699700

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] <i>In vivo</i> evidence for possible up-regulating roles of lysophosphatidic acid around fertilization in rats2018

    • Author(s)
      Takeda T, Shirasaka M, Sugiyama M, Terashima R, Kawaminami M, Kurusu S.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 80 Issue: 1 Pages: 41-48

    • DOI

      10.1292/jvms.17-0354

    • NAID

      130006300859

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Annexin A1 is a novel target gene of gonadotropin-releasing hormone in LβT2 gonadotrope cells2018

    • Author(s)
      Fungbun N, Tungmahasuk D, Terashima R, Kurusu S, Kawaminami M
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 80 Issue: 1 Pages: 116-124

    • DOI

      10.1292/jvms.17-0569

    • NAID

      130006321252

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Possible role of PPARγ in the negative regulation of ovulatory cascade and luteal development in rats2017

    • Author(s)
      Funahashi R, Sakamoto T, Taguchi N, Naiki R, Kawaminami M, Kurusu S
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 79 Issue: 6 Pages: 1043-1051

    • DOI

      10.1292/jvms.17-0162

    • NAID

      130007331444

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prolactin suppression of Gonadotropin releasing hormone initiation of mammary gland involution in female rats.2016

    • Author(s)
      Rieanrakwong D, Laoharatchatathanin T, Terashima R, Yonezawa T, Kurusu S, Hasegawa Y, Kawaminami M.
    • Journal Title

      Endocrinol

      Volume: 157(7) Issue: 7 Pages: 2750-2758

    • DOI

      10.1210/en.2016-1180

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Type-dependent differences in Fas expression and phagocytes distribution in rat corpora lutea during natural regression: an immunohistochemical evidence2016

    • Author(s)
      Satoh H, Yoshio H, Kawaminami M, Kurusu S
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 78 Issue: 12 Pages: 1771-1777

    • DOI

      10.1292/jvms.16-0199

    • NAID

      130005286405

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Augmentation of gonadotropin-releasing hormone receptor expression in the post-lactational mammary tissues of rats2016

    • Author(s)
      Terashima R, Laoharatchatathanin T, Kurusu S, Kawaminami M
    • Journal Title

      J Reprod Dev

      Volume: 62(5) Issue: 5 Pages: 495-499

    • DOI

      10.1262/jrd.2016-035

    • NAID

      130005431262

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Autophagy in corpus luteum as a possibly critical mechanism for rodent pregnancy and parturition.2018

    • Author(s)
      Kurusu S, Ishiwata Y, Oishi Y, Oka S, Yoshio H, Terashima R, Kawaminami M.
    • Organizer
      FEBS2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ラットの妊娠黄体におけるオートファジー機構の発現とその役割2018

    • Author(s)
      浅川晃士、石渡友梨,大石泰彰,岡翔太, 杉山真言、寺島涼太、汾陽光盛、久留主志朗
    • Organizer
      日本繁殖生物学会上田大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Augmentation of Nr4a3 Expression by GnRH and Its Suppressive Effect on FSH Beta Subunit (Fshb) Expression2018

    • Author(s)
      Terashima R, Ikeo M, Nagao D, Saigo T, Kurusu S, Kawaminami M
    • Organizer
      51st Annual Meeting of the Society for the Study of Reproduction
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新規のGonadotropin releasing hormone (GnRH)感受性たんぱく質アネキシンANXA12018

    • Author(s)
      汾陽光盛、Numfa Fungbun、寺島涼太、田中優希、久留主志朗
    • Organizer
      アネキシン研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 新規アネキシンA5関連転写因子Nr4a3の卵胞刺激ホルモン(FSH)特異的発現調節2018

    • Author(s)
      寺島涼太、久留主志朗、汾陽光盛
    • Organizer
      アネキシン研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Physiological relevance of kisspeptin/metastin, neurokinin B, dynorphin and GnRH in granulosa cells of rats2017

    • Author(s)
      Tungmahasuk D , Terashima R, Kurusu S, Kawaminami M
    • Organizer
      Kisspeptin2017 Brain and beyond
    • Place of Presentation
      Orlando (USA)
    • Year and Date
      2017-03-30
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 顆粒層細胞に発現するキスペプチン関連遺伝子の相互作用2017

    • Author(s)
      汾陽光盛, ダンマハス・ドアンラッツ, 寺島涼太, 久留主志朗
    • Organizer
      第21回日本生殖内分泌学会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪府豊中市)
    • Year and Date
      2017-01-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Augmentation of granulosa cell expression of kisspeptin/metastin, neurokinin B, dynorphin and GnRH by hCG: interrelationship between peptides and effects on progesterone synthesis in female rats2017

    • Author(s)
      Doungrut Tungmahasuk, Ryota Terashima, Shiro Kurusu, Mitsumori Kawaminami
    • Organizer
      the 99th Annual Meeting of the Endocrine Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] GnRH Yields Membrane Particles Containing Annexin A5 (ANXA5) from Gonadotrophs and Their Enhancement of LH Release2017

    • Author(s)
      Fungbun N, Sugiyama M, Terashima R, Kurusu S, Kawaminami M
    • Organizer
      the 99th Annual Meeting of the Endocrine Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] GnRH-ANXA5 suppression of progesterone synthesis and cell growth in the primary culture of granulosa cells2017

    • Author(s)
      Doungrut Tungmahasuk, Ryota Terashima, Shiro Kurusu, Mitsumori Kawaminami
    • Organizer
      International conference on annexins
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Involvement of ANXA5 in Gonadotrophin releasing hormone (GnRH) action in the endocrine pancreas2017

    • Author(s)
      Kawaminami M, Terashima R, Kurusu S
    • Organizer
      International conference on annexins
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Autotaxin (ATX) in the circulating blood in pregnant rats: multiple sources and possible regulatory role in parturition2017

    • Author(s)
      Shirasaka M, Masuda K, Toda M, Sugiyama M, Terashima R, Kawaminami M, Kurusu S
    • Organizer
      Fourth World Congress of Reproductive Biology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Luteinizing hormone stimulation of GnRH expression in the testicular interstitial cells2017

    • Author(s)
      Kawaminami M, Sekine H, Yamasaki K, Wakai M, Hirose H, Amano K, Terashima R, Kurusu S
    • Organizer
      Fourth World Congress of Reproductive Biology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pancreatic GnRH is essential for constitutive expression of insulin in islet b cells2017

    • Author(s)
      Kawaminami M, Terashima R, Kurusu S
    • Organizer
      the 99th Annual Meeting of the Endocrine Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Prolactin decreases mast cell number in the ovary of female rats2017

    • Author(s)
      Kawaminami M, Laoharatchatathanin T, Terashima R, Kurusu S
    • Organizer
      FASEB meeting on Growth Hormone/Prolactin Family in Biology and Disease
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] The expression of Nr4a3 is augmented by Gonadotrophin releasing hormone (GnRH) and suppressed by ANXA5 in the pituitary gonadotroph: Inhibitory action of Nr4a3 on follicle stimulating hormone βsubunit expression2017

    • Author(s)
      Terashima R, Kurusu S, Kawaminami M
    • Organizer
      International Conference on Annexins
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Gonadotrophin releasing hormone (GnRH) stimulation of extracellular vesicle formation containing ANXA5 from pituitary gonadotrophs2017

    • Author(s)
      Fungbun N, Sugiyama M, Terashima R, Kurusu S, Kawaminami M
    • Organizer
      International Conference on Annexins
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 発情前期ラットの下垂体における性腺刺激ホルモン放出ホルモン(GnRH)による核内受容体Nr4a3の発現促進2017

    • Author(s)
      寺島涼太、池尾真人、長尾大喜、久留主志朗、汾陽光盛
    • Organizer
      第160回日本獣医学会
    • Related Report
      2017 Research-status Report
  • [Presentation] ラットの排卵カスケードと黄体発育に対するPPARγ の負の調節作用2017

    • Author(s)
      久留主志朗、船橋諒平、坂本貴信、田口範人、内木諒介、寺島涼太、汾陽光盛
    • Organizer
      第160回日本獣医学会
    • Related Report
      2017 Research-status Report
  • [Presentation] GnRH stimulation of Annexin A1 (ANXA1) mRNA expression in the pituitary gonadotroph2016

    • Author(s)
      Fungbun N, Gotoh Y, Koumi Y, Terashima R, Kurusu S, Kawaminami M
    • Organizer
      第41回日本比較内分泌学会
    • Place of Presentation
      北里大学(神奈川県相模原市)
    • Year and Date
      2016-12-09
    • Related Report
      2016 Research-status Report
  • [Presentation] Lysophosphatidic acid may contribute to increasing the fertilization rate in the microenvironment of rat oviducts2016

    • Author(s)
      Kurusu S, Terashima R, Kawaminami M
    • Organizer
      Ovarian Club VIII
    • Place of Presentation
      Paris (France)
    • Year and Date
      2016-11-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 顆粒層細胞におけるメタスチン/キスペプチン、ニューロキニンB(NKB)とダイノルフィンmRNAの発現と相互関係2016

    • Author(s)
      ダンマハス ドアンラッツ, 寺島涼太, 久留主志朗, 汾陽光盛
    • Organizer
      第109回日本繁殖生物学会
    • Place of Presentation
      麻布大学(神奈川県相模原市)
    • Year and Date
      2016-09-12
    • Related Report
      2016 Research-status Report
  • [Presentation] 膵島における性腺刺激ホルモン放出ホルモン(GnRH)の局所作用2016

    • Author(s)
      汾陽光盛, 長場優梨, 中山絵梨子, 寺島涼太, 久留主志朗
    • Organizer
      第159回日本獣医学会
    • Place of Presentation
      日本大学(神奈川県藤沢市)
    • Year and Date
      2016-09-06
    • Related Report
      2016 Research-status Report
  • [Presentation] Augmentation of Nr4a3 expression in the anterior pituitary gland precedes the preovulatory LH surge in ovarian steroids dependent manner2016

    • Author(s)
      Terashima R Ikeo M Saigo T Kurusu S Kawaminami M
    • Organizer
      ISPGRS 2016
    • Place of Presentation
      ホノルル(ハワイ)
    • Year and Date
      2016-09-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Gonadotropin releasing hormone (GnRH) stimulation of annexin A5 and insulin mRNA expression in islet of Langerhans2016

    • Author(s)
      Kawaminami M Terashima R Kurusu S
    • Organizer
      ISPGRS 2016
    • Place of Presentation
      ホノルル(ハワイ)
    • Year and Date
      2016-09-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膵島でのインスリン発現に対する性腺刺激ホルモン放出ホルモン(GnRH)の局所作用2016

    • Author(s)
      長場優梨, 中山絵梨子, 寺島涼太, 久留主志朗, 汾陽光盛
    • Organizer
      第29回北里大学バイオサイエンスフォーラム
    • Place of Presentation
      北里大学薬学部(東京都港区)
    • Year and Date
      2016-08-04
    • Related Report
      2016 Research-status Report
  • [Presentation] 性腺刺激ホルモン放出ホルモン(GnRH)によるアネキシンA1発現の促進2016

    • Author(s)
      後藤 庸, 小海 優, 寺島涼太, 久留主志朗, 汾陽光盛
    • Organizer
      第29回北里大学バイオサイエンスフォーラム
    • Place of Presentation
      北里大学薬学部(東京都港区)
    • Year and Date
      2016-08-04
    • Related Report
      2016 Research-status Report
  • [Presentation] 性腺刺激ホルモン放出ホルモン(GnRH)による核内オーファン受容体Nr4a3発現の促進2016

    • Author(s)
      西郷智貴, 寺島涼太, 久留主志朗, 汾陽光盛
    • Organizer
      第29回北里大学バイオサイエンスフォーラム
    • Place of Presentation
      北里大学薬学部(東京都港区)
    • Year and Date
      2016-08-04
    • Related Report
      2016 Research-status Report
  • [Presentation] 下垂体前葉における核内受容体Nr4a3のラット性周期に伴う特異的変動2016

    • Author(s)
      池尾真人, 寺島涼太, 久留主志朗, 汾陽光盛
    • Organizer
      第29回北里大学バイオサイエンスフォーラム
    • Place of Presentation
      北里大学薬学部(東京都港区)
    • Year and Date
      2016-08-04
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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