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A research group led by Associate Professor NAKAMURA Wataru (Laboratory of Oral Chronobiology, Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University), through collaborative research with UCLA, Meiji University, and Ritsumeikan University, verified the causal correlation between the biological clock and age-related infertility.

The reproductive function of females weakens with age, with irregularities of the menstrual cycle and infertility presenting themselves by the time females reach menopause, but the factors acting in this transitional period were not clear. This group discovered that mice missing the gene that controls circadian rhythm (Cry-KO mice) showed irregularities in the estrous cycle and infertility of mice in the early aging process otherwise capable of giving birth (8~12 months of age, equivalent to the mid-30s~40s in humans).

Through this research, it is hoped that a "circadian timing strategy" will be established in order to improve infertility by leading a life with consideration for an aging circadian clock through efforts such as alleviating the common misalignment of life rhythm between weekdays and weekends.


Female reproductive function changes during aging with the estrous cycle becoming more irregular during the transition to menopause. We found that intermittent shifts of the light-dark cycle disrupted regularity of estrous cycles in middle-aged female mice, whose estrous cycles were regular under unperturbed 24-hr light-dark cycles. Although female mice deficient in Cry1 or Cry2, the core components of the molecular circadian clock, exhibited regular estrous cycles during youth, they showed accelerated senescence characterized by irregular and unstable estrous cycles and resultant infertility in middle age. Notably, tuning the period length of the environmental light-dark cycles closely to the endogenous one inherent in the Cry-deficient females restored the regularity of the estrous cycles and, consequently, improved fertility in middle age. These results suggest that reproductive potential can be strongly influenced by age-related changes in the circadian system and normal reproductive functioning can be rescued by the manipulation of environmental timing signals.

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To learn more about this research, please view the full research report entitled "Recovery from Age-Related Infertility under Environmental Light-Dark Cycles Adjusted to the Intrinsic Circadian Period" at this page of the Cell Reports website.

Related Link

Laboratory of Oral Chronobiology, Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University

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