The Circadian Clock, Nutritional Signals and Reproduction: A Close Relationship

Abstract

The circadian rhythm, which is necessary for reproduction, is controlled by clock genes. In the mouse uterus, the oscillation of the circadian clock gene has been observed. The transcription of the core clock gene period (Per) and cryptochrome (Cry) is activated by the heterodimer of the transcription factor circadian locomotor output cycles kaput (Clock) and brain and muscle Arnt-like protein-1 (Bmal1). By binding to E-box sequences in the promoters of Per1/2 and Cry1/2 genes, the CLOCK-BMAL1 heterodimer promotes the transcription of these genes. Per1/2 and Cry1/2 form a complex with the Clock/Bmal1 heterodimer and inactivate its transcriptional activities. Endometrial BMAL1 expression levels are lower in human recurrent-miscarriage sufferers. Additionally, it was shown that the presence of BMAL1-depleted decidual cells prevents trophoblast invasion, highlighting the importance of the endometrial clock throughout pregnancy. It is widely known that hormone synthesis is disturbed and sterility develops in Bmal1-deficient mice. Recently, we discovered that animals with uterus-specific Bmal1 loss also had poor placental development, and these mice also had intrauterine fetal death. Furthermore, it was shown that time-restricted feeding controlled the uterine clock’s circadian rhythm. The uterine clock system may be a possibility for pregnancy complications, according to these results. We summarize the most recent research on the close connection between the circadian clock and reproduction in this review.

Circle(s) of Life: The Circadian Clock from Birth to Death

“…These glucose rhythms reflected the maternal phase. Subsequent studies on mothers with Bmal1 deficiency and SCN lesions confirmed this finding [ 14 , 15 , 16 ]. Intriguingly, studies on female mice with double clock gene mutations showed that the fetal clock rhythm remains unchanged [ 17 ].…”

Circadian characteristics of term and preterm labors

“…We did not study the role of oxytocin and melatonin in the circadian regulation of birth onset, even though we know they play an important role as emphasized by others 28 . The parallel upregulation of myometrial receptors for melatonin and oxytocin at the time of labor onset underscores the importance of the melatonin signal for uterine contractions in the human parturition 29 , 30 . Interestingly, the recurring nocturnal signal provided by circulating melatonin to the uterus is ineffective for preterm pregnancy.…”

An Evolutionary Perspective on the Genetics of Anorexia Nervosa

“…This includes ARNTL, a major component of the circadian clock system (53,54). In animal models, knock-out or reduced expression of ARNTL have been associated with altered circadian rhythms, body weight, alterations in locomotor activity 16 and eating behaviours, delayed puberty and infertility, cognitive deficits and shortened lifespan (54)(55)(56). Given their role in energy homeostasis and their mutual exclusivity, sleep patterns and eating behaviors are closely related; however, studies on the clinical association between AN and sleep disorders are scarce.…”

“…Existing evidence suggests that sleep problems, including insomnia, are common in people with EDs (57–60) and that sleep disruptions can worsen the severity of AN (60,61). Poor sleep and altered circadian rhythms have also been linked to metabolic dysregulation and obesity (62,63), and to woman’s reproductive health (55,56). One might therefore wonder whether the circadian cycle might be a key element linking AN, BMI and puberty, and whether this phenotype might have conferred some sort of evolutionary advantage.…”