As a discipline, chronobiology has come of age in the last 25 years. There has been an exponential increase in our understanding of the molecular mechanism underlying circadian rhythms of gene expression, physiology, and behavior. While the mammalian clock mechanism has not yet been fully described, most of the primary gears have probably been identified; however, there remains a large submerged portion of this physiological iceberg. What is the extent of "clock-controlled gene" expression in the myriad cell types in mammals? What are the cell specific physiological processes that depend either directly or indirectly on the clock? These questions remain largely unanswered, but recent advances suggest a substantial link between basic clock function and physiology in several systems. In the reproductive system, there has been a recent surge in research on molecular clock function in neuroendocrine and endocrine tissues. This makes sense a priori, given the established link between the circadian clock, behavior (including reproductive behavior), and endocrine physiology. By understanding the role of the clock in basic mammalian reproductive physiology, we can begin to explore its role in the onset and progression of diseases that negatively affect fertility. Advances in this area will certainly yield novel insights into the etiology of these disorders and may provide new and exciting avenues for clinical research in reproduction and fertility.
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"Well before it was determined that peripheral tissues were composed of cell-based oscillators , it was postulated that tissue autonomous clocks could contribute to the timing of hormone synthesis and secretion (Andrews, 1971; Andrews and Folk, 1964; Ungar and Halberg, 1962 ). Since the cloning of the first mammalian circadian clock gene (King et al., 1997) and the determination that clock genes are global regulators of cellular function (Albrecht, 2012 ), considerable evidence has accumulated linking the molecular clock to endocrine physiology (Bass and Takahashi, 2010; Huang et al., 2011; Kalsbeek et al., 2012; Prasai et al., 2011; Sellix and Menaker, 2011; Tonsfeldt and Chappell, 2012; Williams and Kriegsfeld, 2012). These discoveries have stimulated interest in the impact of chronodisruption in all its forms on endocrine physiology (Bass and Takahashi, 2010; Mahoney, 2010 ). "
[Show abstract][Hide abstract]ABSTRACT: Rhythmic events in the female reproductive system depend on the coordinated and synchronized activity of multiple neuroendocrine and endocrine tissues. This coordination is facilitated by the timing of gene expression and cellular physiology at each level of the hypothalamo-pituitary-ovarian (HPO) axis, including the basal hypothalamus and forebrain, the pituitary gland, and the ovary. Central to this pathway is the primary circadian pacemaker in the suprachiasmatic nucleus (SCN) that, through its myriad outputs, provides a temporal framework for gonadotropin release and ovulation. The heart of the timing system, a transcription-based oscillator, imparts SCN pacemaker cells and a company of peripheral tissues with the capacity for daily oscillations of gene expression and cellular physiology. Although the SCN sits comfortably at the helm, peripheral oscillators (such as the ovary) have undefined but potentially critical roles. Each cell type of the ovary, including theca cells, granulosa cells, and oocytes, harbor a molecular clock implicated in the processes of follicular growth, steroid hormone synthesis, and ovulation. The ovarian clock is influenced by the reproductive cycle and diseases that perturb the cycle and/or follicular growth can disrupt the timing of clock gene expression in the ovary. Chronodisruption is known to negatively affect reproductive function and fertility in both rodent models and women exposed to shiftwork schedules. Thus, influencing clock function in the HPO axis with chronobiotics may represent a novel avenue for the treatment of common fertility disorders, particularly those resulting from chronic circadian disruption.
Full-text · Article · Nov 2014 · Journal of Biological Rhythms
[Show abstract][Hide abstract]ABSTRACT: The aim of this study was to examine the daily hypothalamic mRNA expression profiles for two core circadian regulatory proteins, CLOCK2 and PER1, and for two neuropeptides that regulate wakefulness and food intake, OX and NPY, in goldfish. The profiles were determined for fish at different nutritional states (i.e. fed or unfed on sampling day) and held at different photoperiods (i.e. 16L:8D photoperiod vs. constant light LL). Our results show that under a 16L:8D photoperiod, both fed and unfed goldfish exhibit clear antiphasic daily rhythms of hypothalamic Clock2 and Per1 mRNA expression levels, whereas under LL, daily Clock2 rhythms are seen in both fed and unfed fish while significant rhythms of Per1 mRNA expression only persist in unfed fish. In fish held under 16L:8D, but not under LL, there was significantly higher Per1 expression in fed fish at feeding time than in unfed fish. Daily variations in hypothalamic OX mRNA expression levels with peaks observed prior to both feeding time and the onset of darkness, were displayed under a 16L:8D photoperiod, whereas exposure to LL resulted in lower expression levels with no significant daily variations. Fish held under LL, but not under 16L:8D, showed significant daily variations in NPY mRNA expression with a peak prior to feeding time. Taken together, our results suggest that the mRNA expression of both appetite-regulating and circadian proteins display daily variations and that these patterns can be affected by external cues such as feeding and photoperiod.
No preview · Article · May 2012 · Comparative biochemistry and physiology. Part A, Molecular & integrative physiology
[Show abstract][Hide abstract]ABSTRACT: Current scientific evidence suggests that the systemic immune response is affected by exposure to light. During the past century man has been exposed for the first time in evolution to light at night, as well as increasing ultraviolet radiation through depletion of the ozone layer in our atmosphere. These ecological changes have enhanced the impact of light on our systemic immune response. We will review the effect of light on the systemic immune response with particular emphasis on ocular immunity.
Visible light is now recognized to be important in the maintenance of immune privilege within the eye; however, little is known about the mechanism through which this effect occurs. Recent studies suggest that the generation of regulatory T cells involved in immune privilege within the eye is dependent on retinoic acid formation by retinal pigment epithelial cells. Light is also important in modulation of multiple pathways including adjustment of circadian rhythm and production of vitamin D.
Light regulates our biologic systems in many different ways. Its effect on the systemic immune response suggests that it is important in maintaining health, as well as in the induction of disease. A better understanding of the interaction of light with our biologic systems may allow new preventive measures to avoid disease and novel forms of treatment.
No preview · Article · Aug 2012 · Current Opinion in Allergy and Clinical Immunology