Circadian clocks are all but ubiquitous in nature. Circadian rhythms, those biological rhythms with a period at or near 24h, are found in most, if not all, physiological systems ranging from cellular physiology and biochemistry to whole animal physiology. The mechanism controlling these oscillations is a now well-understood molecular oscillator composed of an autoregulatory transcriptional-translational feedback loop. This loop consists of interacting "clock gene" transcriptional regulators that facilitate precision through an elegant temporal scheme of positive and negative gene expression.

Our lab and others have recently determined that the circadian clock mechanism is present in the cells of the ovarian follicle. Further, we have determined that the ovary maintains an "endogenous" pattern of sensitivity to gonadotrophins that does not appear to be dependent on the timing of the LH surge or a fully developed endocrine and neuroendocrine system. These data, together with the data from other labs, suggests that the ovarian clock may play a substantial role in the timing of events in the ovary, related to both the ovulatory response to gonadotrophins and the timing of steroidogenesis.

The Sellix laboratory is currently focused on two distinct but interrelated facets of this research by asking two fundamental questions:

1) Does "clock-controlled" gene expression in the ovary, more specifically the various ovarian cell types, play a substantial role in the timing of ovarian physiology and more specifically the timing of ovulation and/or steroid hormone biosynthesis

2) Do disease states that negatively impact reproductive function (e.g. PCOS, etc.) do so by altering the timing of clock gene or clock-controlled genes in the tissues of the hypothalamo-pituitary-ovarian axis? Further, is phase-synchrony among these oscillators (or lack thereof) a contributing factor to the onset and progression of disease?

• Sellix MT, Evans JA, Leise TL, Castanon-Cervantes O, Hill DD, DeLisser P, Block GD, Menaker M, Davidson AJ. Aging differentially affects the re-entrainment response of central and peripheral circadian oscillators. J Neurosci. 2012 Nov 14; 32(46):16193-202.
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• Sellix MT, Menaker M. Circadian clocks in mammalian reproductive physiology: effects of the "other" biological clock on fertility. Discov Med. 2011 Apr; 11(59):273-81.
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• Pezuk P, Mohawk JA, Yoshikawa T, Sellix MT, Menaker M. Circadian organization is governed by extra-SCN pacemakers. J Biol Rhythms. 2010 Dec; 25(6):432-41.
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• Sellix MT, Menaker M. Circadian clocks in the ovary. Trends Endocrinol Metab. 2010 Oct; 21(10):628-36.
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• Sellix MT, Currie J, Menaker M, Wijnen H. Fluorescence/luminescence circadian imaging of complex tissues at single-cell resolution. J Biol Rhythms. 2010 Jun; 25(3):228-32.
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• Lundkvist GB, Sellix MT, Nygård M, Davis E, Straume M, Kristensson K, Block GD. Clock gene expression during chronic inflammation induced by infection with Trypanosoma brucei brucei in rats. J Biol Rhythms. 2010 Apr; 25(2):92-102.
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• Sellix MT, Yoshikawa T, Menaker M. A circadian egg timer gates ovulation. Curr Biol. 2010 Mar 23; 20(6):R266-7.
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• Nakamura TJ, Sellix MT, Kudo T, Nakao N, Yoshimura T, Ebihara S, Colwell CS, Block GD. Influence of the estrous cycle on clock gene expression in reproductive tissues: effects of fluctuating ovarian steroid hormone levels. Steroids. 2010 Mar; 75(3):203-12.
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• Yoshikawa T, Sellix M, Pezuk P, Menaker M. Timing of the ovarian circadian clock is regulated by gonadotropins. Endocrinology. 2009 Sep; 150(9):4338-47.
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• Nakamura TJ, Sellix MT, Menaker M, Block GD. Estrogen directly modulates circadian rhythms of PER2 expression in the uterus. Am J Physiol Endocrinol Metab. 2008 Nov; 295(5):E1025-31.
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• Davidson AJ, Sellix MT, Daniel J, Yamazaki S, Menaker M, Block GD. Chronic jet-lag increases mortality in aged mice. Curr Biol. 2006 Nov 7; 16(21):R914-6.
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• Egli M, Bertram R, Toporikova N, Sellix MT, Blanco W, Freeman ME. Prolactin secretory rhythm of mated rats induced by a single injection of oxytocin. Am J Physiol Endocrinol Metab. 2006 Mar; 290(3):E566-72.
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• Sellix MT, Egli M, Poletini MO, McKee DT, Bosworth MD, Fitch CA, Freeman ME. Anatomical and functional characterization of clock gene expression in neuroendocrine dopaminergic neurons. Am J Physiol Regul Integr Comp Physiol. 2006 May; 290(5):R1309-23.
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• Sellix MT, Egli M, Henderson RP, Freeman ME. Ovarian steroid hormones modulate circadian rhythms of neuroendocrine dopaminergic neuronal activity. Brain Res. 2004 Apr 16; 1005(1-2):164-81.
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• Egli M, Bertram R, Sellix MT, Freeman ME. Rhythmic secretion of prolactin in rats: action of oxytocin coordinated by vasoactive intestinal polypeptide of suprachiasmatic nucleus origin. Endocrinology. 2004 Jul; 145(7):3386-94.
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• Kanyicska B, Sellix MT, Freeman ME. Autocrine regulation of prolactin secretion by endothelins throughout the estrous cycle. Endocrine. 2003 Feb-Mar; 20(1-2):53-8.
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• Sellix MT, Freeman ME. Circadian rhythms of neuroendocrine dopaminergic neuronal activity in ovariectomized rats. Neuroendocrinology. 2003 Jan; 77(1):59-70.
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• Gerhold LM, Sellix MT, Freeman ME. Antagonism of vasoactive intestinal peptide mRNA in the suprachiasmatic nucleus disrupts the rhythm of FRAs expression in neuroendocrine dopaminergic neurons. J Comp Neurol. 2002 Aug 19; 450(2):135-43.
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• Kanyicska B, Sellix MT, Freeman ME. Autocrine regulation of prolactin secretion by endothelins: a permissive role for estradiol. Endocrine. 2001 Nov; 16(2):133-7.
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• Johnson F, Sellix M. Reorganization of a telencephalic motor region during sexual differentiation and vocal learning in zebra finches. Brain Res Dev Brain Res. 2000 Jun 30; 121(2):253-63.
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