Circadian clock disruption and changes in light-dark cycles could be behind age-related fertility issues and may offer potential treatment targets, findings from an early animal study published in Cell Reports suggest.
Nana Takasu, PhD, of Osaka University in Japan and colleagues examined the effect of altering daily light-dark cycles on reproductive function in young- and middle-aged mice. In middle-aged mice, the researchers found that intermittently shifting light-dark cycles disrupted estrous cycle regularity.
Among mice that were genetically altered to lack a functioning circadian clock (Cry1 or Cry2 deficient), younger mice exhibited regular estrous cycles, regardless of the shifting cycle, whereas middle-aged mice showed accelerated infertility compared with age-matched wild mice.
Previous research has shown that the menstrual cycle in female mammals is affected by the region of the brain, called the suprachiasmatic nucleus (SCN), which controls the circadian clock. Takasu and colleagues suggest that desynchronization between Cry and other "clock genes" (Per, Bmal1 and Clock) that regulate the circadian rhythm of the HPG axis (which controls the estrous cycle) may contribute to infertility, along with an inability for the SCN to signal GnRH nuerons.
The results indicate that, although aging mammals are susceptible to reproductive dysfunction when changes occur in SCN signaling and the circadian clock, these effects might be reversed. Although corresponding studies are needed in humans, ensuring harmony between internal and environmental rhythms may help improve fertility.
"In modern society, females are exposed to many challenging perturbations in the environment that might play a role in fertility difficulties--we now live with high light levels in the evening, and our sleep cycle is disrupted by shift work or crossing time zones," said study co-author Gene Block, of the University of California Los Angeles. "The ability to rescue reproductive function by altering the light schedule in a rodent model suggests that improvements in 'circadian hygiene' — for example, reductions in evening illumination, more regular meal timing, or avoiding rotating shiftwork or schedules that lead to irregular sleep — may all be important remedies for reproductive difficulty."
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.