Circadian rhythms and reproduction

There is a growing recognition that the circadian timing system, in particular recently discovered clock genes, plays a major role in a wide range of physiological systems. Microarray studies, for example, have shown that the expression of hundreds of genes changes many fold in the suprachiasmatic nucleus, liver heart and kidney. In this review, we discuss the role of circadian rhythmicity in the control of reproductive function in animals and humans. Circadian rhythms and clock genes appear to be involved in optimal reproductive performance, but there are sufficient redundancies in their function that many of the knockout mice produced do not show overt reproductive failure. Furthermore, important strain differences have emerged from the studies especially between the variousClock(CircadianLocomotorOutputCycleKaput) mutant strains. Nevertheless, there is emerging evidence that the primary clock genes,ClockandBmal1(Brain andMuscleARNT-like protein 1, also known asMop3), strongly influence reproductive competency. The extent to which the circadian timing system affects human reproductive performance is not known, in part, because many of the appropriate studies have not been done. With the role ofClockandBmal1in fertility becoming clearer, it may be time to pursue the effect of polymorphisms in these genes in relation to the various types of infertility in humans.

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Metabolic disturbances: role of the circadian timing system and sleep

Diabetology International ◽

10.1007/s13340-016-0279-6 ◽

2016 ◽

Vol 8 (1) ◽

pp. 14-22 ◽

Cited By ~ 1

Author(s):

Navin Adhikary ◽

Santosh Lal Shrestha ◽

Jia Zhong Sun

Keyword(s):

Metabolic Disturbances ◽

Circadian Timing ◽

Timing System ◽

Circadian Timing System

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Independence of Circadian Timing from Cell Division in Cyanobacteria

Journal of Bacteriology ◽

10.1128/jb.183.8.2439-2444.2001 ◽

2001 ◽

Vol 183 (8) ◽

pp. 2439-2444 ◽

Cited By ~ 69

Author(s):

Tetsuya Mori ◽

Carl Hirschie Johnson

Keyword(s):

Gene Expression ◽

Cell Division ◽

Circadian Clock ◽

Clock Gene ◽

Circadian Clock Gene ◽

Circadian Timing ◽

Wide Range ◽

Timing System ◽

Circadian Timing System ◽

Cell Division Timing

ABSTRACT In the cyanobacterium Synechococcus elongatus, cell division is regulated by a circadian clock. Deletion of the circadian clock gene, kaiC, abolishes rhythms of gene expression and cell division timing. Overexpression of the ftsZ gene halted cell division but not growth, causing cells to grow as filaments without dividing. The nondividing filamentous cells still exhibited robust circadian rhythms of gene expression. This result indicates that the circadian timing system is independent of rhythmic cell division and, together with other results, suggests that the cyanobacterial circadian system is stable and well sustained under a wide range of intracellular conditions.

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Role of the renal circadian timing system in maintaining water and electrolytes homeostasis

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2011.06.037 ◽

2012 ◽

Vol 349 (1) ◽

pp. 51-55 ◽

Cited By ~ 32

Author(s):

Dmitri Firsov ◽

Natsuko Tokonami ◽

Olivier Bonny

Keyword(s):

Circadian Timing ◽

Timing System ◽

Circadian Timing System

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Role of the suprachiasmatic nuclei in the circadian timing system of the squirrel monkey. II. Light-dark cycle entrainment

Brain Research ◽

10.1016/0006-8993(84)90838-2 ◽

1984 ◽

Vol 300 (2) ◽

pp. 285-293 ◽

Cited By ~ 15

Author(s):

H. Elliot Albers ◽

Ralph Lydic ◽

Martin C. Moore-ede

Keyword(s):

Squirrel Monkey ◽

Suprachiasmatic Nuclei ◽

Dark Cycle ◽

Circadian Timing ◽

Timing System ◽

Circadian Timing System

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Maternal circadian rhythms and the programming of adult health and disease

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00248.2017 ◽

2018 ◽

Vol 314 (2) ◽

pp. R231-R241 ◽

Cited By ~ 13

Author(s):

Tamara J. Varcoe ◽

Kathryn L. Gatford ◽

David J. Kennaway

Keyword(s):

Circadian Rhythms ◽

Well Being ◽

International Travel ◽

Adult Health ◽

Circadian Timing ◽

Timing System ◽

Circadian Timing System ◽

Delayed Sleep Phase Disorder ◽

Delayed Sleep Phase ◽

The Impact

The in utero environment is inherently rhythmic, with the fetus subjected to circadian changes in temperature, substrates, and various maternal hormones. Meanwhile, the fetus is developing an endogenous circadian timing system, preparing for life in an external environment where light, food availability, and other environmental factors change predictably and repeatedly every 24 h. In humans, there are many situations that can disrupt circadian rhythms, including shift work, international travel, insomnias, and circadian rhythm disorders (e.g., advanced/delayed sleep phase disorder), with a growing consensus that this chronodisruption can have deleterious consequences for an individual’s health and well-being. However, the impact of chronodisruption during pregnancy on the health of both the mother and fetus is not well understood. In this review, we outline circadian timing system ontogeny in mammals and examine emerging research from animal models demonstrating long-term negative implications for progeny health following maternal chronodisruption during pregnancy.

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Circadian rhythms of temperature and activity in obese and lean Zucker rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.269.5.r1038 ◽

1995 ◽

Vol 269 (5) ◽

pp. R1038-R1043 ◽

Cited By ~ 11

Author(s):

D. M. Murakami ◽

B. A. Horwitz ◽

C. A. Fuller

Keyword(s):

Circadian Rhythms ◽

Female Rats ◽

Zucker Rats ◽

Circadian Regulation ◽

Circadian Timing ◽

Lighting Conditions ◽

Timing System ◽

Circadian Timing System ◽

Obese Zucker Rats ◽

Normal Light

The circadian timing system is important in the regulation of feeding and metabolism, both of which are aberrant in the obese Zucker rat. This study tested the hypothesis that these abnormalities involve a deficit in circadian regulation by examining the circadian rhythms of body temperature and activity in lean and obese Zucker rats exposed to normal light-dark cycles, constant light, and constant dark. Significant deficits in both daily mean and circadian amplitude of temperature and activity were found in obese Zucker female rats relative to lean controls in all lighting conditions. However, the circadian period of obese Zucker rats did not exhibit differences relative to lean controls in either of the constant lighting conditions. These results indicate that although the circadian regulation of temperature and activity in obese Zucker female rats is in fact depressed, obese rats do exhibit normal entrainment and pacemaker functions in the circadian timing system. The results suggest a deficit in the process that generates the amplitude of the circadian rhythm.

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Melatonin, Clock Genes, and Mammalian Reproduction: What Is the Link?

International Journal of Molecular Sciences ◽

10.3390/ijms222413240 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13240

Author(s):

Amnon Brzezinski ◽

Seema Rai ◽

Adyasha Purohit ◽

Seithikurippu R. Pandi-Perumal

Keyword(s):

Circadian Rhythm ◽

Circadian Rhythms ◽

Molecular Clock ◽

Reproductive Performance ◽

Clock Genes ◽

Current Knowledge ◽

Reproductive Function ◽

The Body ◽

Molecular Clocks ◽

Biological Regulation

Physiological processes and behaviors in many mammals are rhythmic. Recently there has been increasing interest in the role of circadian rhythmicity in the control of reproductive function. The circadian rhythm of the pineal hormone melatonin plays a role in synchronizing the reproductive responses of animals to environmental light conditions. There is some evidence that melatonin may have a role in the biological regulation of circadian rhythms and reproduction in humans. Moreover, circadian rhythms and clock genes appear to be involved in optimal reproductive performance. These rhythms are controlled by an endogenous molecular clock within the suprachiasmatic nucleus (SCN) in the hypothalamus, which is entrained by the light/dark cycle. The SCN synchronizes multiple subsidiary oscillators (clock genes) existing in various tissues throughout the body. The basis for maintaining the circadian rhythm is a molecular clock consisting of transcriptional/translational feedback loops. Circadian rhythms and clock genes appear to be involved in optimal reproductive performance. This mini review summarizes the current knowledge regarding the interrelationships between melatonin and the endogenous molecular clocks and their involvement in reproductive physiology (e.g., ovulation) and pathophysiology (e.g., polycystic ovarian syndrome).

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Evidence that pain sensitivity is rhythmic in humans, mainly driven by the endogenous circadian system and little by sleep

10.1101/2020.12.23.424196 ◽

2020 ◽

Author(s):

I Daguet ◽

V Raverot ◽

D Bouhassira ◽

C Gronfier

Keyword(s):

Pain Management ◽

Pain Sensitivity ◽

Time Of Day ◽

Circadian System ◽

Circadian Timing ◽

Healthy Humans ◽

Wide Range ◽

Timing System ◽

Circadian Timing System ◽

Sensitivity To Pain

AbstractPain intensity has been reported to fluctuate during the day in some experimental and clinical conditions, but the mechanisms underlying these fluctuations are unknown. Although the circadian timing system is known to regulate a wide range of physiological functions, its implication in pain regulation is unknown. We show here, using highly controlled laboratory constant routine conditions, that pain sensitivity is rhythmic over the 24-hours and strongly controlled by the endogenous circadian timing system. We find that pain sensitivity follows a sinusoidal circadian rhythmicity, with a maximum in the middle of the night and a minimum in the afternoon. We also find a weak homeostatic control of pain sensitivity, with a linear increase over the 34 hours of prolonged wakefulness, which parallels that of sleep pressure. Using mathematical modelling, we describe that the circadian system accounts for 80% of the full magnitude of pain sensitivity over the 24 hours, and that sleep-related processes account for only 20%. This result reveals that nocturnal analgesia is predominantly induced by the circadian system and has been wrongly attributed only to sleep. Our findings highlight the need to consider the time of day in pain assessment, and suggest that personalized circadian medicine may be a promising approach to pain management.Significance statementWe discovered that sensitivity to pain is rhythmic in healthy humans, that sensitivity is maximal at night and minimal in the afternoon. Contrarily to the current thinking that sleep is the best painkiller, we find that the 24-h rhythmicity of sensitivity to pain is mainly controlled by a biological circadian clock in our body, and very little by our sleep. Our article reveals the neurobiological mechanisms involved in driving the rhythmicity of pain perception in humans, with the main time-piece located in the brain (the suprachiasmatic nuclei in the hypothalamus). Our findings challenge the current vision of pain physiology, and reveal the need to consider time-of-day and internal biological time for pain evaluation and pain management.

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