Circadian Clocks in Mammalian Reproductive Physiology: Effects of the "Other" Biological Clock on Fertility

Department of Biology, University of Virginia, Charlottesville, 22904, USA.
Discovery medicine (Impact Factor: 3.63). 04/2011; 11(59):273-81.
Source: PubMed


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.

Download full-text


Available from: Michael T. Sellix, Feb 13, 2015
  • [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
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Circadian clocks have been described in each tissue of the hypothalamo-pituitary-ovarian axis. Although a role for the clock in the timing of ovulation is indicated, the impact of diseases that disrupt fertility on clock function or the clocks' role in the etiology of these pathologies has yet to be fully appreciated. Polycystic ovary syndrome (PCOS) is a particularly devastating endocrinopathy, affecting approximately 10 of women at childbearing age. Common features of PCOS are a polycystic ovary, amenorrhea, and excess serum androgen. Approximately 40% of these women have metabolic syndrome, including hyperinsulinemia, dyslipidemia, and hyperleptinemia. It has been suggested that excess androgen is a critical factor in the etiology of PCOS. We have examined the effects of androgen excess during puberty on the phase of circadian clocks in tissues of the metabolic and hypothalamo-pituitary-ovarian axes. Female period1-luciferase (per1-luc) rats were exposed to androgen (5α-dihydrotestosterone [DHT]) or placebo for 4-6 weeks (short term) or 9-15 weeks (long term). As expected, DHT-treated animals gained more weight than controls and had disrupted estrous cycles. At the end of treatment, tissues, including the liver, lung, kidney, white adipose, cornea, pituitary, oviduct, and ovarian follicles, were cultured, and per1-luc expression in each was recorded. Analysis of per1-luc expression revealed that DHT exposure increased phase distribution of multiple oscillators, including ovarian follicles, liver, and adipose, and altered phase synchrony between animals. These data suggest that excess androgen during puberty, a common feature of PCOS, negatively affects internal circadian organization in both the reproductive and metabolic axes.
    Full-text · Article · Feb 2013 · Endocrinology
Show more