Many biological processes, including sleep and wakefulness as well as feeding and metabolism, have a 24-hour rhythmicity. The circadian rhythms that underlie these patterns are controlled in the brain by a molecular clock that has a period of approximately 24 hours. By studying the Clock mutant mouse, which has a mutation in a gene that regulates the internal clock, researchers have shown that normal female reproductive function depends on an intact biological clock.

It had previously been known that removal of the part of the brain responsible for circadian behavior resulted in abnormal reproduction. In the new work, Howard Hughes Medical Institute investigator Dr. Joseph S. Takahashi, Northwestern University professor Dr. Teresa H. Horton, and graduate student Brooke H. Miller found that the disruption of the Clock gene resulted in abnormal estrous cycles (the mouse equivalent of human menstrual cycles), primarily due to a defect in the control of hormone release by the brain. The researchers also found that Clock mutant females exhibited high rates of mid-gestation pregnancy failure, a process that had not previously been linked to circadian rhythms.

These experiments increase the understanding of the way complex physiology can be regulated by circadian rhythms. More broadly, the findings have implications for human infertility; it has been shown that women who work swing-shifts are more susceptible than normal to irregular menstrual cycles and miscarriage.

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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
9-Aug-2004