title: Recovery from Age-Related Infertility under Environmental Light-Dark Cycles Adjusted to the Intrinsic Circadian Period.
abstract: 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.
authors: Laboratory of Oral Chronobiology, Graduate School of Dentistry, Osaka University, Suita, Osaka 565-0871, Japan.
authors: Nana N
authors: NN
authors: Takasu
authors: Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki, Kanagawa 214-8571, Japan.
authors: Takahiro J
authors: TJ
authors: Nakamura
authors: Department of Mechanical Engineering, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan.
authors: Isao T
authors: IT
authors: Tokuda
authors: Department of Radiation Biology and Medical Genetics, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors: Takeshi
authors: T
authors: Todo
authors: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA 90024-1759, USA. Electronic address: gblock@conet.ucla.edu.
authors: Gene D
authors: GD
authors: Block
authors: Laboratory of Oral Chronobiology, Graduate School of Dentistry, Osaka University, Suita, Osaka 565-0871, Japan; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan. Electronic address: wataru@dent.osaka-u.ac.jp.
authors: Wataru
authors: W
authors: Nakamura
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002940:Circadian Rhythm; D056931:Cryptochromes / Q000235:genetics; D030762:Estrous Cycle / Q000235:genetics / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017440:Photoperiod
chemical_list: C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; D056931:Cryptochromes