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Mathematical model for circadian control of estrus cycles and its implication to infertility treatment

Research Project

Project/Area Number 16K00343
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Soft computing
Research InstitutionRitsumeikan University

Principal Investigator

Tokuda Isao  立命館大学, 理工学部, 教授 (00261389)

Co-Investigator(Kenkyū-buntansha) 石村 憲意  立命館大学, 理工学部, 助教 (50779072)
Research Collaborator Nakamura Wataru  
Nakamura Takahiro  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords性周期 / 概日リズム / 視交叉上核 / 同期 / 引込み / 振動子 / データ解析 / 数理モデル / 不妊治療
Outline of Final Research Achievements

In mammals, estrous cycles are not only regulated by the hypothalamus-pituitary-gonadal axis but they also require an appropriately timed signal from the suprachiasmatic nucleus, which forms the central circadian pacemaker. Towards understanding the circadian control of estrus cycles, we studied behavioral rhythms of wild-type female mice. We found that phase response properties of the circadian system were independent of the estrous stages, implying that intrinsic photic entrainment system is not influenced by the estrous cycle. We also confirmed that shift-work disrupts circadian rhythmicity and consequently induces irregular estrous cycles. We finally constructed a prototype mathematical model for circadian system that regulates estrous cycles. Decrease in the timing signal gave rise to very long or irregular estrous cycles. The present study may provide insights into an improved life style as a possible treatment for infertility.

Academic Significance and Societal Importance of the Research Achievements

行動リズムの位相応答特性には、性周期依存が見られないことから、メスの概日行動を決めているのは中枢時計の視交叉上核であり、性周期の中枢への影響は弱いことが分かった。これは、中枢時計を整えることが、性周期の周期性を保つには重要という考えを支持している。また、昼夜勤のローテーションは時差ぼけを生じ、性周期を乱すため、妊娠を望む女性には避けるべき勤務形態であることが改めて浮き彫りとなった。排卵を促進し妊娠に至るには,規則性のある性周期を保つことが重要であり、本研究で明らかとなった概日時計による性周期制御の知見は,晩婚化が進み少子化問題を抱える先進国で深刻化する不妊治療の糸口を与えると期待される。

Report

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

    (25 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (16 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 13 results,  Open Access: 8 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) Book (1 results)

  • [Int'l Joint Research] フンボルト大学理論生物学科(ドイツ)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Reducing the complexity of mathematical models for the plant circadian clock by distributed delays2019

    • Author(s)
      Tokuda Isao T.、Akman Ozgur E.、Locke James C.W.
    • Journal Title

      Journal of Theoretical Biology

      Volume: 463 Pages: 155-166

    • DOI

      10.1016/j.jtbi.2018.12.014

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Highly Heterogeneous Excitatory Connections Require Less Amount of Noise to Sustain Firing Activities in Cortical Networks2018

    • Author(s)
      Kada Hisashi、Teramae Jun-nosuke、Tokuda Isao T.
    • Journal Title

      Frontiers in Computational Neuroscience

      Volume: 12 Pages: 1-12

    • DOI

      10.3389/fncom.2018.00104

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coherency of circadian rhythms in the SCN is governed by the interplay of two coupling factors2018

    • Author(s)
      Tokuda Isao T.、Ono Daisuke、Honma Sato、Honma Ken-Ichi、Herzel Hanspeter
    • Journal Title

      PLOS Computational Biology

      Volume: 14 Issue: 12 Pages: 1006607-1006607

    • DOI

      10.1371/journal.pcbi.1006607

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Normal peripheral circadian phase in the old-old with abnormal circadian behavior2018

    • Author(s)
      Yamaguchi Ai、Tatsumoto Muneto、Matsumura Ritsuko、Endo Takuyuki、Hirata Koichi、Tokuda Isao、Akashi Makoto
    • Journal Title

      Genes to Cells

      Volume: 23 Issue: 10 Pages: 849-859

    • DOI

      10.1111/gtc.12633

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Photic phase-response curves for cycling female mice2018

    • Author(s)
      Mizuta Shuto、Sugiyama Mizuki、Tokuda Isao T.、Nakamura Wataru、Nakamura Takahiro J.
    • Journal Title

      Hormones and Behavior

      Volume: 105 Pages: 41-46

    • DOI

      10.1016/j.yhbeh.2018.07.008

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Coordination of robust single cell rhythms in the Arabidopsis circadian clock via spatial waves of gene expression2018

    • Author(s)
      Gould Peter D、Domijan Mirela、Greenwood Mark、Tokuda Isao T、Rees Hannah、Kozma-Bognar Laszlo、Hall Anthony JW、Locke James CW
    • Journal Title

      eLife

      Volume: 7

    • DOI

      10.7554/elife.31700

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Multicellularity enriches the entrainment of Arabidopsis circadian clock2017

    • Author(s)
      Masuda Kosaku、Kitaoka Ryota、Ukai Kazuya、Tokuda Isao T.、Fukuda Hirokazu
    • Journal Title

      Science Advances

      Volume: 3 Issue: 10

    • DOI

      10.1126/sciadv.1700808

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of different light-dark schedules on estrous cycle in mice, and implications for mitigating the adverse impact of night work2017

    • Author(s)
      Yoshinaka Kiichi、Yamaguchi Ai、Matsumura Ritsuko、Node Koichi、Tokuda Isao、Akashi Makoto
    • Journal Title

      Genes Cells

      Volume: 22 Issue: 10 Pages: 876-884

    • DOI

      10.1111/gtc.12522

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transition of phase response properties and singularity in the circadian limit cycle of cultured cells2017

    • Author(s)
      Koinuma Satoshi、Kori Hiroshi、Tokuda Isao T.、Yagita Kazuhiro、Shigeyoshi Yasufumi
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 7 Pages: 1-16

    • DOI

      10.1371/journal.pone.0181223

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential contribution of tandem circadian enhancers to nonlinear oscillations in clock gene expression2017

    • Author(s)
      Isao T. Tokuda, Akihiko Okamoto, Ritsuko Matsumura, Toru Takumi, Makoto Akashi
    • Journal Title

      Mol. Biol. Cell.

      Volume: 28 Issue: 17 Pages: 2333-2342

    • DOI

      10.1091/mbc.e17-02-0129

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] New insights into olivo-cerebellar circuits for learning from a small training sample2017

    • Author(s)
      Tokuda Isao T、Hoang Huu、Kawato Mitsuo
    • Journal Title

      Current Opinion in Neurobiology

      Volume: 46 Pages: 58-67

    • DOI

      10.1016/j.conb.2017.07.010

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Salt-inducible kinase 3 regulates the mammalian circadian clock by destabilizing PER2 protein2017

    • Author(s)
      Naoto Hayasaka, Arisa Hirano, Yuka Miyoshi, Isao T. Tokuda, Hikari Yoshitane, Junichiro Matsuda, Yoshitaka Fukada
    • Journal Title

      eLife

      Volume: 6

    • DOI

      10.7554/elife.24779

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Experimental study on synchronization of sound-coupled electronic metronomes2017

    • Author(s)
      Hisashi Kada, Kei Kondo, Shota Sumino, Isao T. Tokuda
    • Journal Title

      Nonlinear Theory and Its Applications, IEICE

      Volume: 8 Pages: 15-24

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Experimental Verification of Desynchronization of Neurons via Heterogeneous Inhibitory Connections2017

    • Author(s)
      Hisashi Kada, Isao T. Tokuda
    • Journal Title

      IEICE Transactions on Fundamentals of Electronics, Communications and Computer Sciences

      Volume: E100.A Issue: 2 Pages: 611-618

    • DOI

      10.1587/transfun.E100.A.611

    • NAID

      130005306018

    • ISSN
      0916-8508, 1745-1337
    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Validating Stereo-Endoscopy with a Synthetic Vocal Fold Model2016

    • Author(s)
      K.A.Stevens, R. Shimamura, H. Imagawa, K.-I. Sakakibara, I.T.Tokuda
    • Journal Title

      Acta Acustica united with Acustica

      Volume: 102 Issue: 4 Pages: 745-751

    • DOI

      10.3813/aaa.918990

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effective Suppression of Pathological Synchronization in Cortical Networks by Highly Heterogeneous Distribution of Inhibitory Connections2016

    • Author(s)
      Hisashi Kada, Jun-nosuke Teramae, and Isao T. Tokuda
    • Journal Title

      Frontiers in Computational Neuroscience

      Volume: 10 Pages: 109-109

    • DOI

      10.3389/fncom.2016.00109

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] A mathematical model for transient dissociation of Per1 and Bmal1 rhythms in the suprachiasmatic nuclues2018

    • Author(s)
      Christoph Schmal, Isao T. Tokuda, Daisuke Ono, Sato Honma, Ken-ichi Honma, and Hanspeter Herzel
    • Organizer
      第25回日本時間生物学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mathematical modeling of dual coupling mechanisms in the suprachiasmatic nucleus2018

    • Author(s)
      Isao Tokuda, Daisuke Ono, Sato Honma, Ken-ichi Honma, Hanspeter Herzel
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Mathematical modeling of cellular circadian network with dual coupling mechanisms in the SCN2017

    • Author(s)
      Isao Tokuda, Daisuke Ono, Sato Honma, Ken-ichi Honma, Hanspeter Herzel
    • Organizer
      Gordon research conference on Chronobiology
    • Related Report
      2017 Research-status Report
  • [Presentation] Mathematical model for cellular circadian network having dual coupling mechanisms in the SCN2017

    • Author(s)
      徳田功, 小野大輔, 本間さと, 本間研一, Herzel Hanspeter
    • Organizer
      第24回日本時間生物学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Supression of pathological synchronization in cortical network2016

    • Author(s)
      Isao Tokuda, Hisashi Kada, Junnosuke Teramae
    • Organizer
      複雑コミュニケーションサイエンス(CCS)研究会
    • Place of Presentation
      京都産業大学(京都府・京都市)
    • Year and Date
      2016-11-04
    • Related Report
      2016 Research-status Report
  • [Presentation] Hyperacuity Bayesian technique to enhance temporal resolution of two-photon recording of complex spikes of cerebellar Purkinje cells2016

    • Author(s)
      Huu Thien Hoang, Okito Yamashita, Isao T. Tokuda, Kazuo Kitamura, Masa-Aki Sato, Mitsuo Kawato, Keisuke Toyama
    • Organizer
      39th Annual meeting of Japan Neuroscience Society
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-07-21
    • Related Report
      2016 Research-status Report
  • [Presentation] 抑制性神経細胞の不均一な入力がもたらす脱同期とその電子回路への実装2016

    • Author(s)
      嘉田 久嗣, 徳田 功
    • Organizer
      第60回システム制御情報学会研究発表講演会
    • Place of Presentation
      京都テルサ(京都府・京都市)
    • Year and Date
      2016-05-27
    • Related Report
      2016 Research-status Report
  • [Book] 機械力学の基礎:力学への入門2017

    • Author(s)
      宮野尚哉,徳田功
    • Total Pages
      175
    • Publisher
      数理工学社
    • ISBN
      9784864810456
    • Related Report
      2017 Research-status Report

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

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