An official website of the United States government
The estrous cycle regulates rhythms of locomotor activity, body temperature, and circadian gene expression. In female mice, activity increases on the night of proestrus, when elevated estrogens cause ovulation. Exogenous estradiol regulates eating behavior rhythms in female mice fed a high-fat diet, but it is unknown whether endogenous estrogens regulate eating rhythms. In this study, we investigated whether diurnal and circadian eating behavior rhythms change systematically across the estrous cycle. We first studied diurnal eating behavior rhythms in female C57BL/6J mice in 12L:12D. Estrous cycle stages were determined by vaginal cytology while eating behavior and wheel revolutions were continuously measured. The mice had regular 4- to 5-day estrous cycles. Consistent with prior studies, the greatest number of wheel revolutions occurred on the night of proestrus into estrus when systemic levels of estrogens peak. The amplitude, or robustness, of the eating behavior rhythm also fluctuated with 4- to 5-day cycles and peaked primarily during proestrus or estrus. The phases of eating behavior rhythms fluctuated, but not at 4- or 5-day intervals, and phases did not correlate with estrous cycle stages. After ovariectomy, the eating behavior rhythm amplitude fluctuated at irregular intervals. In constant darkness, the amplitude of the circadian eating behavior rhythm peaked every 4 or 5 days and coincided with the circadian day that had the greatest number of wheel revolutions, a marker of proestrus. These data suggest that fluctuations of ovarian hormones across the estrous cycle temporally organize the robustness of circadian eating behavior rhythms so that it peaks during ovulation and sexual receptivity.
more »
« less
Long days restore regular estrous cyclicity in mice lacking circadian rhythms
Many female mammals have recurring cycles of ovulation and sexual behaviors that are regulated by reproductive hormones and confer reproductive success. In addition to sexual behaviors, circadian behavioral rhythms of locomotor activity also fluctuate across the estrous cycle in rodents. Moreover, there is a bidirectional relationship between circadian rhythms and estrous cyclicity since mice with disrupted circadian rhythms also have compromised estrous cycles resulting in fewer pregnancies. In the present study, we assessed whether extending day length, which alters circadian rhythms, normalizes estrous cyclicity in mice. We found that Period (Per) 1/2/3 triple knockout (KO) mice, that have disabled canonical molecular circadian clocks, have markedly disrupted estrous cycles. Surprisingly, extending the day length by only 2 hours per day restored regular 4- or 5-day estrous cycles to Per1/2/3 KO mice. Longer days also induced consistent 4-day, rather than 5-day, estrous cycles in wild-type C57BL/6J mice. These data demonstrate that extending daytime light exposure could be used for enhancing reproductive success.
more »
« less
- Award ID(s):
- 2045267
- PAR ID:
- 10505224
- Publisher / Repository:
- Elsevier
- Date Published:
- Journal Name:
- Heliyon
- Volume:
- 9
- Issue:
- 6
- ISSN:
- 2405-8440
- Page Range / eLocation ID:
- e16970
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Disruptions to circadian rhythms in mammals are associated with alterations in their physiological and mental states. Circadian rhythms are currently analyzed in the time domain using approaches such as actograms, thus failing to appreciate their time-localized characteristics, time-varying nature and multiscale dynamics. In this study, we apply time-resolved analysis to investigate behavioral rhythms in Per1/2/3 knockout (KO) mice and their changes following methamphetamine administration, focusing on circadian (around 24 h), low-frequency ultradian (around 7 h), high-frequency ultradian (around 30 min), and circabidian (around 48 h) oscillations. In the absence of methamphetamine, Per1/2/3 KO mice in constant darkness exhibited a dominant, ∼7 h oscillation. We demonstrate that methamphetamine exposure restores the circadian rhythm, although the frequency of the methamphetamine sensitive circadian oscillator varied considerably compared to the highly regular wild-type circadian rhythm. Additionally, methamphetamine increased multiscale activity and induced a circabidian oscillation in the Per1/2/3 KO mice. The information transfer between oscillatory modes, with frequencies around circadian, low-frequency ultradian and high-frequency ultradian activity, due to their mutual couplings, was also investigated. For Per1/2/3 KO mice in constant darkness, the most prevalent coupling was between low and high-frequency ultradian activity. Following methamphetamine administration, the coupling between the circadian and high-frequency ultradian activity became dominant. In each case, the direction of information transfer was between the corresponding phases from the slower to faster oscillations. The time-varying nature of the circadian rhythm exhibited in the absence of Per1/2/3 genes and following methamphetamine administration may have profound implications for health and disease.more » « less
-
null (Ed.)Abstract Shift work, performed by approximately 21 million Americans, is irregular or unusual work schedule hours occurring after 6:00 pm. Shift work has been shown to disrupt circadian rhythms and is associated with several adverse health outcomes and chronic diseases such as cancer, gastrointestinal and psychiatric diseases and disorders. It is unclear if shift work influences the complications associated with certain infectious agents, such as pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility resulting from genital chlamydial infection. We used an Environmental circadian disruption (ECD) model mimicking circadian disruption occurring during shift work, where mice had a 6-h advance in the normal light/dark cycle (LD) every week for a month. Control group mice were housed under normal 12/12 LD cycle. Our hypothesis was that compared to controls, mice that had their circadian rhythms disrupted in this ECD model will have a higher Chlamydia load, more pathology and decreased fertility rate following Chlamydia infection. Results showed that, compared to controls, mice that had their circadian rhythms disrupted (ECD) had higher Chlamydia loads, more tissue alterations or lesions, and lower fertility rate associated with chlamydial infection. Also, infected ECD mice elicited higher proinflammatory cytokines compared to mice under normal 12/12 LD cycle. These results imply that there might be an association between shift work and the increased likelihood of developing more severe disease from Chlamydia infection.more » « less
-
Circadian rhythms are internal processes repeating approximately every 24 hours in living organisms. The dominant circadian pacemaker is synchronized to the environmental light-dark cycle. Other circadian pacemakers, which can have noncanonical circadian mechanisms, are revealed by arousing stimuli, such as scheduled feeding, palatable meals and running wheel access, or methamphetamine administration. Organisms also have ultradian rhythms, which have periods shorter than circadian rhythms. However, the biological mechanism, origin, and functional significance of ultradian rhythms are not well-elucidated. The dominant circadian rhythm often masks ultradian rhythms; therefore, we disabled the canonical circadian clock of mice by knocking out Per1/2/3 genes, where Per1 and Per2 are essential components of the mammalian light-sensitive circadian mechanism. Furthermore, we recorded wheel-running activity every minute under constant darkness for 272 days. We then investigated rhythmic components in the absence of external influences, applying unique multiscale time-resolved methods to analyze the oscillatory dynamics with time-varying frequencies. We found four rhythmic components with periods of ∼17 h, ∼8 h, ∼4 h, and ∼20 min. When the ∼17-h rhythm was prominent, the ∼8-h rhythm was of low amplitude. This phenomenon occurred periodically approximately every 2-3 weeks. We found that the ∼4-h and ∼20-min rhythms were harmonics of the ∼8-h rhythm. Coupling analysis of the ridge-extracted instantaneous frequencies revealed strong and stable phase coupling from the slower oscillations (∼17, ∼8, and ∼4 h) to the faster oscillations (∼20 min), and weak and less stable phase coupling in the reverse direction and between the slower oscillations. Together, this study elucidated the relationship between the oscillators in the absence of the canonical circadian clock, which is critical for understanding their functional significance. These studies are essential as disruption of circadian rhythms contributes to diseases, such as cancer and obesity, as well as mood disorders.more » « less
-
Conspicuous sexual signals come with costs and benefits. Such signals increase reproductive success but may also reduce survival or viability. It has recently been suggested that non-signal traits may alleviate some of those costs (termed “compensatory traits”). In this perspective piece, we argue that biological rhythms should be considered in the milieu of compensatory traits, as they can reduce the natural selection burden of signaling. This may be particularly true for the many sexual signals that are ephemeral (i.e., only periodically present like a courtship dance). Biological rhythms (e.g., circadian and circannual rhythms) are ubiquitous in nature and help organisms perform the right activity at the right time—this includes the timing of many sexual signals and reproductive traits. Timing itself may, in fact, reduce the costs of such sexual signals. Here, we review sexual signals that are governed by biological rhythms and discuss how signal modality and type (ornament, weapon, dominance trait) account for differences in how chronobiology may act as a compensatory trait. We then consider how biologists might examine the untested role of chronobiology as a compensatory trait and set forth compelling questions for future work.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1016/j.heliyon.2023.e16970
