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

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K00343
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Soft computing
• Research Institution: Ritsumeikan 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
• Keywords: 性周期 / 概日リズム / 視交叉上核

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.

Free Research Field

非線形動力学

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。