Role of core circadian clock genes in hormone release and target tissue sensitivity in the reproductive axis

Aritro Sen, Hanne M Hoffmann, Aritro Sen, Hanne M Hoffmann

Abstract

Precise timing in hormone release from the hypothalamus, the pituitary and ovary is critical for fertility. Hormonal release patterns of the reproductive axis are regulated by a feedback loop within the hypothalamic-pituitary-gonadal (HPG) axis. The timing and rhythmicity of hormone release and tissue sensitivity in the HPG axis is regulated by circadian clocks located in the hypothalamus (suprachiasmatic nucleus, kisspeptin and GnRH neurons), the pituitary (gonadotrophs), the ovary (theca and granulosa cells), the testis (Leydig cells), as well as the uterus (endometrium and myometrium). The circadian clocks integrate environmental and physiological signals to produce cell endogenous rhythms generated by a transcriptional-translational feedback loop of transcription factors that are collectively called the "molecular clock". This review specifically focuses on the contribution of molecular clock transcription factors in regulating hormone release patterns in the reproductive axis, with an emphasis on the female reproductive system. Specifically, we discuss the contributions of circadian rhythms in distinct neuronal populations of the female hypothalamus, the molecular clock in the pituitary and its overall impact on female and male fertility.

Keywords: Circadian rhythms; Clock genes; Estrogen; Gene transcription; Gonadotropin-releasing hormone; Hormone release; Hypothalamic-pituitary-gonadal axis; Kisspeptin; Ovary; Suprachiasmatic nucleus.

Copyright © 2019 Elsevier B.V. All rights reserved.

Figures

Figure 1.. Circadian rhythms exist throughout the…
Figure 1.. Circadian rhythms exist throughout the reproductive axis.
Fertility is regulated by the hypothalamic-pituitary-gonadal axis. The presence of a functional molecular clock, composed of clock transcription factors including BMAL1, CRY1/2/3, CLOCK and PER1/2 has been identified at all levels of the reproductive axis (indicated by the sinusoidal symbol). The absence of core clock genes, such as Per, Cry, Bmal1 and Clock are all associated with impaired fertility. To align peripheral clocks to the time-of-day, a time signal from the SCN is transmitted to peripheral clocks. At the level of the hypothalamus the SCN projects directly onto kisspeptin and GnRH neurons to modulate their activity. Increased release of GnRH is mandatory for the LH surge, and the combination of SCN-afferents on GnRH neurons with increased estrogen levels and kisspeptin signaling allows for correct GnRH neuron firing. Abbreviations: AVP: arginine vasopressin, Bmal1: aryl hydrocarbon receptor nuclear translocator like 1, Clock: circadian locomotor output cycles kaput, Cry: cryptochrome, FSH: follicle stimulating hormone, GnRH: gonadotropin-releasing hormone, LH: luteinizing hormone, Per: period circadian clock, SCN: suprachiasmatic nucleus, VIP: vasoactive intestinal peptide.
Figure 2.. The molecular clock generates cell-endogenous…
Figure 2.. The molecular clock generates cell-endogenous circadian rhythms and circadian gene expression of clock-controlled genes (CCGs).
Cell endogenous circadian rhythms are generated by a fine-tuned transcription-translation feedback loop within nucleated cells. The core transcription factors generating these circadian rhythms are the transcription factors CLOCK and BMAL1. CLOCK and BMAL1 form a heterodimer and bind to E-boxes in regulatory regions to promote the expression of clock genes, including Per1/2/3 and Cryl/2, as well as clock controlled genes (Ccg containing E-boxes in their promoters. Per1/2/3 and Cryl/2, along with the Ccgs’ translocate to the nucleus for translation. To generate a circadian rhythm in gene expression, PER1/2/3 and CRY1/2 proteins form a complex and return to the nucleus to inhibit transcription by binding to and inactivating the CLOCK:BMAL1 complex. The stability of PER1/2/3 is regulated by CK1δ, CK1ε, and CK2, enzymes that phosphorylate PERs and promote their degradation. The stability of CRY1/2 is regulated by ubiquitination by FBXL3 and FBXL21. Abbreviations: Bmal1: aryl hydrocarbon receptor nuclear translocator like 1, CCG: clock-controlled genes, CK: casein kinase, Clock: circadian locomotor output cycles kaput, Cry: cryptochrome, FBXL: F-box proteins and Per: period. Adapted with permission from UC San Diego BioClock Studio.
Figure 3.. Regulation of the ovarian clock…
Figure 3.. Regulation of the ovarian clock by gonadotropins.
To maintain optimum ovarian function and normal fertility, the hypothalamus and the pituitary maintain a synchrony with the ovarian clock via endocrine signals involving FSH and LH. The gonadotropins, through regulation of core clock genes like Per and Bmal1, regulate the ovarian circadian clock which in turn controls the expression and timing of expression of genes critical for normal ovarian physiology (Clock controlled genes). Abbreviations: LHr: luteinizing hormone receptor, Cox2: cyclooxygenase 2, StAR: steroidogenic acute regulatory protein, 3b HSD: 3-beta hydroxysteroid dehydrogenase, Cyp11A: cholesterol side-chain cleavage enzyme, Cyp19a: aromatase.

References

    1. Abraham U, et al. (2010). “Coupling governs entrainment range of circadian clocks.” Mol Syst Biol 6: 438.
    1. Abrahamson EE and Moore RY (2001). “Suprachiasmatic nucleus in the mouse: retinal innervation, intrinsic organization and efferent projections.” Brain Res 916(1–2): 172–191.
    1. Adachi S, et al. (2007). “Involvement of anteroventral periventricular metastin/kisspeptin neurons in estrogen positive feedback action on luteinizing hormone release in female rats.” Journal of Reproduction and Development: 0701090061–0701090061.
    1. Alexander MJ, et al. (1985). “Vasoactive intestinal polypeptide effects a central inhibition of pulsatile luteinizing hormone secretion in ovariectomized rats.” Endocrinology 117(5): 2134–2139.
    1. Alvarez J, et al. (2003). “Non-cyclic and developmental stage-specific expression of circadian clock proteins during murine spermatogenesis.” Biology of reproduction 69(1): 81–91.
    1. Alvarez J, et al. (2008). “The circadian clock protein BMAL1 is necessary for fertility and proper testosterone production in mice.” Journal of biological rhythms 23(1): 26–36.
    1. Amano T, et al. (2009). “Expression and functional analyses of circadian genes in mouse oocytes and preimplantation embryos: Cry1 is involved in the meiotic process independently of circadian clock regulation.” Biology of reproduction 80(3): 473–483.
    1. Attarchi M, et al. (2013). “Characteristics of menstrual cycle in shift workers.” Global journal of health science 5(3): 163.
    1. Bae K, et al. (2001). “Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock.” Neuron 30(2): 525–536.
    1. Baker FC and Driver HS (2007). “Circadian rhythms, sleep, and the menstrual cycle.” Sleep Med 8(6): 613–622.
    1. Barbacka-Surowiak G, et al. (2003). “The involvement of suprachiasmatic nuclei in the regulation of estrous cycles in rodents.” Reprod Biol 3(2): 99–129.
    1. Bebas P, et al. (2009). “Circadian clock and output genes are rhythmically expressed in extratesticular ducts and accessory organs of mice.” The FASEB Journal 23(2): 523–533.
    1. Bedont JL, et al. (2014). “Lhx1 controls terminal differentiation and circadian function of the suprachiasmatic nucleus.” Cell Rep 7(3): 609–622.
    1. Beek E v. d., et al. (1999). “Reproductive Neuroendocrinology-Central Administration of Antiserum to Vasoactive Intestinal Peptide Delays and Reduces Luteinizing Hormone and Prolactin Surges in Ovariectomized, Estrogen-Treated.” Neuroendocrinology 69(4): 227–237.
    1. Beesley S, et al. (2015). “Circadian clock regulation of melatonin MTNR1B receptor expression in human myometrial smooth muscle cells.” Molecular human reproduction 21(8): 662–671.
    1. Bittman EL (2016). “Timing in the testis.” Journal of biological rhythms 31(1): 12–36.
    1. Bittman EL (2019). “Circadian Function in Multiple Cell Types Is Necessary for Proper Timing of the Preovulatory LH Surge.” Journal of biological rhythms: 0748730419873511.
    1. Bittman EL, et al. (2003). “Period gene expression in mouse endocrine tissues.” American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 285(3): R561–R569.
    1. Boden MJ and Kennaway DJ (2004). “Reproductive Consequences of Circadian Dysfunction: Fertility in the Bmal1 null mouse.” Reprod. Fertil. Dev 16(9): 280–280.
    1. Boden MJ, et al. (2010). “Reproductive biology of female Bmal1 null mice.” Reproduction 139(6): 1077–1090.
    1. Bosc M (1990). “Photoperiodic regulation of the time of birth in rats: involvement of circadian endogenous mechanisms.” Physiology & behavior 48(3): 441–446.
    1. Brown-Grant K and Raisman G (1977). “Abnormalities in reproductive function associated with the destruction of the suprachiasmatic nuclei in female rats. “ Proceedings of the Royal Society of London. Series B. Biological Sciences 198(1132): 279–296.
    1. Buhr ED and Takahashi JS (2013). “Molecular components of the Mammalian circadian clock.” Handb Exp Pharmacol(217): 3–27.
    1. Chappell PE and Levine JE (2000). “Stimulation of gonadotropin-releasing hormone surges by estrogen. I. Role of hypothalamic progesterone receptors.” Endocrinology 141(4): 1477–1485.
    1. Chappell PE, et al. (2003). “Circadian gene expression regulates pulsatile gonadotropin-releasing hormone (GnRH) secretory patterns in the hypothalamic GnRH-secreting GT1–7 cell line.” Journal of Neuroscience 23(35): 11202–11213.
    1. Chassard D, et al. (2015). “Evidence for a putative circadian kiss-clock in the hypothalamic AVPV in female mice.” Endocrinology 156(8): 2999–3011.
    1. Chemineau P, et al. (1988). “Photoperiodic and melatonin treatments for the control of seasonal reproduction in sheep and goats.” Reproduction Nutrition Développement 28(2B): 409–422.
    1. Chen H, et al. (2013). “FSH induces the development of circadian clockwork in rat granulosa cells via a gap junction protein Cx43-dependent pathway.” American journal of physiology. Endocrinology and metabolism 304(6): E566–575.
    1. Chen H, et al. (2013). “Downregulation of core clock gene Bmal1 attenuates expression of progesterone and prostaglandin biosynthesis-related genes in rat luteinizing granulosa cells.” American journal of physiology. Cell physiology 304(12): C1131–1140.
    1. Choe HK, et al. (2013). “Synchronous activation of gonadotropin-releasing hormone gene transcription and secretion by pulsatile kisspeptin stimulation.” Proceedings of the National Academy of Sciences 110(14): 5677–5682.
    1. Christian CA, et al. (2008). “Classical estrogen receptor a signaling mediates negative and positive feedback on gonadotropin-releasing hormone neuron firing.” Endocrinology 149(11): 5328–5334.
    1. Christian CA and Moenter SM (2008). “Vasoactive intestinal polypeptide can excite gonadotropin-releasing hormone neurons in a manner dependent on estradiol and gated by time of day.” Endocrinology 149(6): 3130–3136.
    1. Christian CA and Moenter SM (2010). “The neurobiology of preovulatory and estradiol-induced gonadotropin-releasing hormone surges.” Endocrine reviews 31(4): 544–577.
    1. Chu A, et al. (2013). “Global but not gonadotrope-specific disruption of Bmal1 abolishes the luteinizing hormone surge without affecting ovulation.” Endocrinology 154(8): 2924–2935.
    1. Chu G, et al. (2012). “Contribution of FSH and triiodothyronine to the development of circadian clocks during granulosa cell maturation.” Am J Physiol Endocrinol Metab 302(6): E645–653.
    1. Chu G, et al. (2011). “Alterations of circadian clockworks during differentiation and apoptosis of rat ovarian cells.” Chronobiol Int 28(6): 477–487.
    1. Chung F-F, et al. (2005). “The associations between menstrual function and life style/working conditions among nurses in Taiwan.” Journal of occupational health 47(2): 149–156.
    1. Clarkson J, et al. (2009). “Postnatal development of an estradiol-kisspeptin positive feedback mechanism implicated in puberty onset.” Endocrinology 150(7): 3214–3220.
    1. Clarkson J, et al. (2017). “Definition of the hypothalamic GnRH pulse generator in mice.” Proceedings of the National Academy of Sciences 114(47): E10216–E10223.
    1. de la Iglesia HO and Schwartz WJ (2006). “Minireview: timely ovulation: circadian regulation of the female hypothalamo-pituitary-gonadal axis.” Endocrinology 147(3): 1148–1153.
    1. Desroziers E, et al. (2010). “Mapping of kisspeptin fibres in the brain of the pro-oestrous rat.” Journal of neuroendocrinology 22(10): 1101–1112.
    1. Dolatshad H, et al. (2005). “Developmental and reproductive performance in circadian mutant mice.” Human reproduction 21(1): 68–79.
    1. Dror T, et al. (2013). “Analysis of multiple positive feedback paradigms demonstrates a complete absence of LH surges and GnRH activation in mice lacking Kisspeptin signaling.” Biol Reprod 88(6): 146.
    1. Duggavathi R, et al. (2008). “Liver receptor homolog 1 is essential for ovulation.” Genes Dev 22(14): 1871–1876.
    1. Dulka E and Moenter S (2019). “SAT-412 Effects of the Ovary and Dihydrotestosterone on Firing Rate of GnRH Neurons in Prenatally Androgenized Mice.” Journal of the Endocrine Society 3(Supplement_1): SAT–412.
    1. Ebenhöh O and Hazlerigg D (2013). “Modelling a molecular calendar: the seasonal photoperiodic response in mammals.” Chaos, Solitons & Fractals 50: 39–47.
    1. Ebihara S, et al. (1986). “Genetic control of melatonin synthesis in the pineal gland of the mouse.” Science 231(4737): 491–493.
    1. Estrada K, et al. (2006). “Elevated KiSS-1 expression in the arcuate nucleus prior to the cyclic preovulatory gonadotrophin-releasing hormone/lutenising hormone surge in the ewe suggests a stimulatory role for kisspeptin in oestrogen-positive feedback.” Journal of neuroendocrinology 18(10): 806–809.
    1. Evans JA, et al. (2012). “Cryl−/− circadian rhythmicity depends on SCN intercellular coupling.” J Biol Rhythms 27(6): 443–452.
    1. Everett JW and Sawyer CH (1950). “A 24-hour periodicity in the “LH-release apparatus” of female rats, disclosed by barbiturate sedation.” Endocrinology 47(3): 198–218.
    1. Fahrenkrug J, et al. (2006). “Diurnal rhythmicity of the clock genes Per1 and Per2 in the rat ovary.” Endocrinology 147(8): 3769–3776.
    1. Fernandez RC, et al. (2016). Fixed or rotating night shift work undertaken by women: implications for fertility and miscarriage Seminars in reproductive medicine, Thieme Medical Publishers.
    1. Foster DL, et al. (2006). “Programming of GnRH feedback controls timing puberty and adult reproductive activity.” Mol Cell Endocrinol 254–255: 109–119.
    1. Gamble KL, et al. (2013). “Shift work and circadian dysregulation of reproduction.” Frontiers in endocrinology 4: 92.
    1. Gibson MJ, et al. (1994). “Continuous gonadotropin-releasing hormone infusion stimulates dramatic gonadal development in hypogonadal female mice.” Biol. Reprod 50(3): 680–685.
    1. Gill JC, et al. (2010). “Reproductive hormone-dependent and-independent contributions to developmental changes in kisspeptin in GnRH-deficient hypogonadal mice.” PloS one 5(7): e11911.
    1. Gillespie JM, et al. (2003). “Expression of circadian rhythm genes in gonadotropin-releasing hormone-secreting GT1–7 neurons.” Endocrinology 144(12): 5285–5292.
    1. Glanowska KM, et al. (2014). “Development of gonadotropin-releasing hormone secretion and pituitary response.” Journal of Neuroscience 34(45): 15060–15069.
    1. Glanowska KM, et al. (2012). “Fast scan cyclic voltammetry as a novel method for detection of real-time gonadotropin-releasing hormone release in mouse brain slices.” Journal of Neuroscience 32(42): 14664–14669.
    1. Gorman M (In Press). “Temporal organization of melatonin signalling in mammals.” Molecular and cellular endocrinology.
    1. Goto M, et al. (1989). “Melatonin content of the pineal gland in different mouse strains.” Journal of pineal research 7(2): 195–204.
    1. Gottsch M, et al. (2006). “Kisspepeptin-GPR54 signaling in the neuroendocrine reproductive axis.” Molecular and cellular endocrinology 254: 91–96.
    1. Greenhill C (2014). “Circadian clock involved in embryo implantation.” Nature Reviews Endocrinology 10(12).
    1. Gu G and Simerly R (1997). “Projections of the sexually dimorphic anteroventral periventricular nucleus in the female rat.” Journal of Comparative Neurology 384(1): 142–164.
    1. Han S-K, et al. (2005). “Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty.” Journal of Neuroscience 25(49): 11349–11356.
    1. Hardeland R, et al. (2006). “Melatonin.” The international journal of biochemistry & cell biology 38(3): 313–316.
    1. Hastings MH, et al. (2019). “The mammalian circadian timing system and the suprachiasmatic nucleus as its pacemaker.” Biology 8(1): 13.
    1. Hatori M, et al. (2014). “Lhx1 maintains synchrony among circadian oscillator neurons of the SCN.” eLife 3: e03357.
    1. He PJ, et al. (2007). “The disruption of circadian clockwork in differentiating cells from rat reproductive tissues as identified by in vitro real-time monitoring system.” J Endocrinol 193(3): 413–420.
    1. He PJ, et al. (2007). “Gonadotropic regulation of circadian clockwork in rat granulosa cells.” Mol Cell Biochem 302(1–2): 111–118.
    1. He PJ, et al. (2007). “Up-regulation of Per1 expression by estradiol and progesterone in the rat uterus.” J Endocrinol 194(3): 511–519.
    1. Herbison AE (2008). “Estrogen positive feedback to gonadotropin-releasing hormone (GnRH) neurons in the rodent: the case for the rostral periventricular area of the third ventricle (RP3V).” Brain research reviews 57(2): 277–287.
    1. Herbison AE (2018). “The gonadotropin-releasing hormone pulse generator.” Endocrinology 159(11): 3723–3736.
    1. Herbison AE, et al. (2007). “Gonadotropin-releasing hormone neuron requirements for puberty, ovulation, and fertility.” Endocrinology 149(2): 597–604.
    1. Hickok JR and Tischkau SA (2010). “In vivo circadian rhythms in gonadotropin-releasing hormone neurons.” Neuroendocrinology 91(1): 110–120.
    1. Hirst JJ, et al. (1993). “Plasma oxytocin and nocturnal uterine activity: maternal but not fetal concentrations increase progressively during late pregnancy and delivery in rhesus monkeys.” American journal of obstetrics and gynecology 169(2): 415–422.
    1. Hoffmann HM, et al. (2019). “Differential CRE Expression in Lhrh-cre and GnRH-cre Alleles and the Impact on Fertility in Otx2-Flox Mice.” Neuroendocrinology 108(4): 328–342.
    1. Hoffmann HM, et al. (2018). “Haploinsufficiency of Homeodomain Proteins Six3, Vax1, and Otx2 Causes Subfertility in Mice via Distinct Mechanisms.” Neuroendocrinology 108(4): 328–335.
    1. Hoffmann HM, et al. (2016). “Deletion of Vax1 from gonadotropin-releasing hormone (GnRH) neurons abolishes GnRH expression and leads to hypogonadism and infertility.” Journal of Neuroscience 36(12): 3506–3518.
    1. Hoffmann HM, et al. (2014).” Heterozygous deletion of ventral anterior homeobox (vaxl) causes subfertility in mice.” Endocrinology. 155(10):4043–53.
    1. Hogenesch JB and Ueda HR (2011). “Understanding systems-level properties: timely stories from the study of clocks.” Nat Rev Genet 12(6): 407–416.
    1. Horvath TL, et al. (1998). “Gender-specific apposition between vasoactive intestinal peptide-containing axons and gonadotrophin-releasing hormone-producing neurons in the rat.” Brain Res 795(1–2): 277–281.
    1. Irwig MS, et al. (2004). “Kisspeptin activation of gonadotropin releasing hormone neurons and regulation of KiSS-1 mRNA in the male rat.” Neuroendocrinology 80(4): 264–272.
    1. Jacobi JS, et al. (2007). “17-Beta-estradiol directly regulates the expression of adrenergic receptors and kisspeptin/GPR54 system in GT1–7 GnRH neurons.” Neuroendocrinology 86(4): 260–269.
    1. Johnson MH, et al. (2002). “Circadian clockwork genes are expressed in the reproductive tract and conceptus of the early pregnant mouse.” Reprod.Biomed.Online 4(2): 140.
    1. Karman BN and Tischkau SA (2006). “Circadian clock gene expression in the ovary: Effects of luteinizing hormone.” Biol Reprod 75(4): 624–632.
    1. Karsch FJ, et al. (1984). Neuroendocrine basis of seasonal reproduction Proceedings of the 1983 Laurentian Hormone Conference, Elsevier.
    1. Kauffman AS, et al. (2007). “Sexual differentiation of Kiss1 gene expression in the brain of the rat.” Endocrinology 148(4): 1774–1783.
    1. Kauffman AS, et al. (2007). “The kisspeptin receptor GPR54 is required for sexual differentiation of the brain and behavior.” Journal of Neuroscience 27(33): 8826–8835.
    1. KKennaway DJ, et al. (2012). “Circadian rhythms and fertility.” Molecular and cellular endocrinology 349(1): 56–61.
    1. Kim JW, et al. (2005). “The orphan nuclear receptor, liver receptor homolog-1, regulates cholesterol side-chain cleavage cytochrome p450 enzyme in human granulosa cells.” J Clin Endocrinol Metab 90(3): 1678–1685.
    1. Kimura F, et al. (1987). “Effects of preoptic injections of gastrin, cholecystokinin, secretin, vasoactive intestinal peptide and PHI on the secretion of luteinizing hormone and prolactin in ovariectomized estrogen-primed rats.” Brain Res 410(2): 315–322.
    1. Klose M, et al. (2011). “Temporal control of spermatogenesis is independent of the central circadian pacemaker in Djungarian hamsters (Phodopus sungorus).” Biology of reproduction 84(1): 124–129.
    1. Knobil E (1980). The neuroendocrine control of the menstrual cycle Proceedings of the 1979 Laurentian Hormone Conference, Elsevier.
    1. Knutsson A (2003). “Health disorders of shift workers.” Occupational medicine 53(2): 103–108.
    1. Ko CH, et al. (2010). “Emergence of noise-induced oscillations in the central circadian pacemaker.” PLoS Biol 8(10): e1000513.
    1. Koike N, et al. (2012). “Transcriptional architecture and chromatin landscape of the core circadian clock in mammals.” Science 338(6105): 349–354.
    1. Kriegsfeld LJ (2013). “Circadian regulation of kisspeptin in female reproductive functioning.” Adv Exp Med Biol 784: 385–410.
    1. Kriegsfeld LJ, et al. (2002). “Vasoactive intestinal polypeptide contacts on gonadotropin-releasing hormone neurones increase following puberty in female rats.” J Neuroendocrinol 14(9): 685–690.
    1. Kumar P and Sait SF (2011). “Luteinizing hormone and its dilemma in ovulation induction.” Journal of human reproductive sciences 4(1): 2.
    1. Labyak S, et al. (2002). “Effects of shiftwork on sleep and menstrual function in nurses.” Health care for women international 23(6–7): 703–714.
    1. Lapatto R, et al. (2007). “Kiss1−/− mice exhibit more variable hypogonadism than Gpr54−/− mice.” Endocrinology 148(10): 4927–4936.
    1. Legan SJ and Karsch FJ (1975). “A daily signal for the LH surge in the rat.” Endocrinology 96(1): 57–62.
    1. Lehman MN, et al. (2013). Neuroanatomy of the kisspeptin signaling system in mammals: comparative and developmental aspects Kisspeptin signaling in reproductive biology, Springer: 27–62.
    1. Lehman MN, et al. (2010). “Anatomy of the kisspeptin neural network in mammals.” Brain Res 1364: 90–102.
    1. Li C, et al. (2017). “Altered expression of miRNAs in the uterus from a letrozole-induced rat PCOS model.” Gene 598: 20–26.
    1. Li L, et al. (2014). “Cooperation of luteinizing hormone signaling pathways in preovulatory avian follicles regulates circadian clock expression in granulosa cell.” Mol Cell Biochem 394(1–2): 31–41.
    1. Liu AC, et al. (2007). “Intercellular coupling confers robustness against mutations in the SCN circadian clock network.” Cell 129(3): 605–616.
    1. Liu Y, et al. (2014). “Loss of BMAL1 in ovarian steroidogenic cells results in implantation failure in female mice.” Proceedings of the National Academy of Sciences 111(39): 14295–14300.
    1. Loh DH, et al. (2014). “Disrupted Reproduction, Estrous Cycle, and Circadian Rhythms in Female Mice Deficient in Vasoactive Intestinal Peptide.” J Biol Rhythms.
    1. Lohstroh PN, et al. (2003). “Bone resorption is affected by follicular phase length in female rotating shift workers.” Environmental health perspectives 111(4): 618–622.
    1. Lowrey PL and Takahashi JS (2011). “Genetics of circadian rhythms in Mammalian model organisms.” Adv Genet 74: 175–230.
    1. Lv S, et al. (2019). “Impaired decidualization caused by downregulation of circadian clock gene BMAL1 contributes to human recurrent miscarriage.” Biology of reproduction.
    1. Ma X, et al. (2004). “Targeted disruption of luteinizing hormone beta-subunit leads to hypogonadism, defects in gonadal steroidogenesis, and infertility.” Proc. Natl. Acad. Sci. USA 101(49): 17294–17299.
    1. Mahoney MM (2010). “Shift work, jet lag, and female reproduction.” Int J Endocrinol 2010: 813764.
    1. Matagne V, et al. (2012). “Thyroid transcription factor 1, a homeodomain containing transcription factor, contributes to regulating periodic oscillations in GnRH gene expression.” J Neuroendocrinol 24(6): 916–929.
    1. McQuillan HJ, et al. (2019). “GnRH pulse generator activity across the estrous cycle of female mice.” Endocrinology 160(6): 1480–1491.
    1. Mereness AL, et al. (2016). “Conditional Deletion of Bmal1 in Ovarian Theca Cells Disrupts Ovulation in Female Mice.” Endocrinology 157(2): 913–927.
    1. Mereness AL, et al. (2015). “Developmental programming by androgen affects the circadian timing system in female mice.” Biol Reprod 92(4): 88.
    1. Mesiano S and Jaffe RB (1997). “Developmental and functional biology of the primate fetal adrenal cortex.” Endocrine reviews 18(3): 378–403.
    1. Messager S, et al. (2005). “Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54.” Proceedings of the National Academy of Sciences 102(5): 1761–1766.
    1. Miller BH, et al. (2004). “Circadian clock mutation disrupts estrous cyclicity and maintenance of pregnancy.” Current biology 14(15): 1367–1373.
    1. Miller BH and Takahashi JS (2013). “Central circadian control of female reproductive function.” Frontiers in endocrinology 4: 195.
    1. Minami Y, et al. (2013). “Mammalian circadian clock: the roles of transcriptional repression and delay.” Handb Exp Pharmacol(217): 359–377.
    1. Moenter SM, et al. (1990). “The estradiol-induced surge of gonadotropin-releasing hormone in the ewe.” Endocrinology 127(3): 1375–1384.
    1. Mongrain V, et al. (2008). “Clock-dependent and independent transcriptional control of the two isoforms from the mouse Rorygene.” Genes to Cells 13(12): 1197–1210.
    1. Morse D, et al. (2003). “No circadian rhythms in testis: Period1 expression is clock independent and developmentally regulated in the mouse.” Molecular endocrinology 17(1): 141–151.
    1. Nakamura TJ, et al. (2010). “Influence of the estrous cycle on clock gene expression in reproductive tissues: effects of fluctuating ovarian steroid hormone levels.” Steroids 75(3): 203–212.
    1. Nakamura TJ, et al. (2008). “Estrogen directly modulates circadian rhythms of PER2 expression in the uterus.” American Journal of Physiology-Endocrinology and Metabolism 295(5): E1025–E1031.
    1. Nitta M, et al. (1999). “CPF: an orphan nuclear receptor that regulates liver-specific expression of the human cholesterol 7alpha-hydroxylase gene.” Proc Natl Acad Sci U S A 96(12): 6660–6665.
    1. Nurminen T (1998). “Shift work and reproductive health.” Scand J Work Environ Health 24 Suppl 3: 28–34.
    1. Oiwa A, et al. (2007). “Synergistic regulation of the mouse orphan nuclear receptor SHP gene promoter by CLOCK-BMAL1 and LRH-1.” Biochem Biophys Res Commun 353(4): 895–901.
    1. Olcese J (2014). “Circadian clocks and pregnancy.” Frontiers in endocrinology 5.
    1. Olcese J, et al. (2003). “Expression and regulation of mPer1 in immortalized GnRH neurons.” Neuroreport 14(4): 613–618.
    1. Olcese J, et al. (2013). “Melatonin and the circadian timing of human parturition.” Reproductive Sciences 20(2): 168–174.
    1. Padilla SL, et al. (2019). “Kisspeptin neurons in the arcuate nucleus of the hypothalamus orchestrate circadian rhythms and metabolism.” Current biology 29(4): 592–604. e594.
    1. Pandolfi EC, et al. (2019). “The Homeodomain Transcription Factors Vax1 and Six6 Are Required for SCN Development and Function.” Molecular Neurobiology. Nov 9.
    1. Pandolfi EC, et al. (2019). “Deletion of the Homeodomain Protein Six6 from GnRH Neurons Decreases GnRH Gene Expression Resulting in Infertility.” Endocrinology. 160(9):2151–2164.
    1. Perrin JS, et al. (2006). “The expression of the clock protein PER2 in the limbic forebrain is modulated by the estrous cycle.” Proceedings of the National Academy of Sciences 103(14): 5591–5596.
    1. Petersen SL, et al. (2003). “Direct and indirect regulation of gonadotropin-releasing hormone neurons by estradiol.” Biology of reproduction 69(6): 1771–1778.
    1. Piet R, et al. (2016). “Vasoactive intestinal peptide excites GnRH neurons in male and female mice.” Endocrinology 157(9): 3621–3630.
    1. Pilorz V and Steinlechner S (2008). “Low reproductive success in Per1 and Per2 mutant mouse females due to accelerated ageing?” Reproduction 135(4): 559.
    1. Ratajczak CK, et al. (2012). “Generation of myometrium-specific Bmal1 knockout mice for parturition analysis.” Reproduction, Fertility and Development 24(5): 759–767.
    1. Ratajczak CK, et al. (2009). “Impaired steroidogenesis and implantation failure in Bmal1−/− mice.” Endocrinology 150(4): 1879–1885.
    1. Reppert SM, et al. (1987). “The circadian-gated timing of birth in rats: disruption by maternal SCN lesions or by removal of the fetal brain.” Brain Res 403(2): 398–402.
    1. Revel FG, et al. (2009). “Melatonin controls seasonal breeding by a network of hypothalamic targets.” Neuroendocrinology 90(1): 1–14.
    1. Richards JS (2001). “Perspective: The ovarian follicle--A perspective in 2001.” Endocrinology 142(6): 2184–2193.
    1. Richards JS, et al. (1998). “Molecular mechanisms of ovulation and luteinization.” Mol Cell Endocrinol 145(1–2): 47–54.
    1. Robertson JL, et al. (2009). “Circadian regulation of Kiss1 neurons: implications for timing the preovulatory gonadotropin-releasing hormone/luteinizing hormone surge.” Endocrinology 150(8): 3664–3671.
    1. Rubel CA, et al. (2012). “Research resource: Genome-wide profiling of progesterone receptor binding in the mouse uterus.” Mol Endocrinol 26(8): 1428–1442.
    1. Samson WK, et al. (1981). “Vasoactive intestinal peptide stimulates luteinizing hormone-releasing hormone release from median eminence synaptosomes.” Regulatory peptides 2(4): 253–264.
    1. Schoeller EL, et al. (2016). “Bmal1 is required for normal reproductive behaviors in male mice.” Endocrinology 157(12): 4914–4929.
    1. Sellix MT (2015). “Circadian clock function in the mammalian ovary.” J Biol Rhythms 30(1): 7–19.
    1. Sellix MT, et al. (2013). “Excess androgen during puberty disrupts circadian organization in female rats.” Endocrinology 154(4): 1636–1647.
    1. Sellix MT, et al. (2010). “A circadian egg timer gates ovulation.” Curr Biol 20(6): R266–267.
    1. Semaan SJ and Kauffman AS (2010). “Sexual differentiation and development of forebrain reproductive circuits.” Curr Opin Neurobiol 20(4): 424–431.
    1. Sharkey JT, et al. (2009). “Melatonin synergizes with oxytocin to enhance contractility of human myometrial smooth muscle cells.” The Journal of Clinical Endocrinology & Metabolism 94(2): 421–427.
    1. Shimizu T, et al. (2011). “Circadian Clock genes Per2 and clock regulate steroid production, cell proliferation, and luteinizing hormone receptor transcription in ovarian granulosa cells.” Biochem Biophys Res Commun 412(1): 132–135.
    1. Simonneaux V, et al. (2017). “Daily rhythms count for female fertility.” Best Practice & Research Clinical Endocrinology & Metabolism 31(5): 505–519.
    1. Singh J and Handelsman DJ (1996). “Neonatal administration of FSH increases Sertoli cell numbers and spermatogenesis in gonadotropin-deficient (hpg) mice.” J. Endocrinol 151(1): 37–48.
    1. Sirois J, et al. (2004). “Cyclooxygenase-2 and its role in ovulation: a 2004 account.” Hum Reprod Update 10(5): 373–385.
    1. Smarr BL, et al. (2013). “Oestrogen-independent circadian clock gene expression in the anteroventral periventricular nucleus in female rats: possible role as an integrator for circadian and ovarian signals timing the luteinising hormone surge.” J Neuroendocrinol 25(12): 1273–1279.
    1. Smarr BL, et al. (2012). “The dorsomedial suprachiasmatic nucleus times circadian expression of Kiss1 and the luteinizing hormone surge.” Endocrinology 153(6): 2839–2850.
    1. Smith JT (2008). “Kisspeptin signalling in the brain: steroid regulation in the rodent and ewe.” Brain research reviews 57(2): 288–298.
    1. Smith JT, et al. (2005). “Regulation of Kiss1 gene expression in the brain of the female mouse.” Endocrinology 146(9): 3686–3692.
    1. Smith JT, et al. (2006). “Kiss1 neurons in the forebrain as central processors for generating the preovulatory luteinizing hormone surge.” Journal of Neuroscience 26(25): 6687–6694.
    1. Smith MJ, et al. (2000). “Localization of the VIP2 receptor protein on GnRH neurons in the female rat.” Endocrinology 141(11): 4317–4320.
    1. Stock D, et al. (2019). “Rotating night shift work and menopausal age.” Human reproduction 34(3): 539–548.
    1. Stojkovic K, et al. (2014). “A central role for ubiquitination within a circadian clock protein modification code.” Frontiers in molecular neuroscience 7: 69.
    1. Sugimoto Y, et al. (2015). “Roles of prostaglandin receptors in female reproduction.” J Biochem 157(2): 73–80.
    1. Tischkau SA, et al. (2011). “The luteinizing hormone surge regulates circadian clock gene expression in the chicken ovary.” Chronobiol Int 28(1): 10–20.
    1. Tonsfeldt KJ, et al. (2019). The Contribution of Bmal1 Expression in the Suprachiasmatic Nucleus to Female Fertility. ENDOExpo.
    1. Tonsfeldt KJ, et al. (2011). “Oestrogen induces rhythmic expression of the Kisspeptin-1 receptor GPR54 in hypothalamic gonadotrophin-releasing hormone-secreting GT1–7
    1. Tonsfeldt KJ, et al. (2019). “The Contribution of the Circadian Gene Bmal1 to Female Fertility and the Generation of the Preovulatory Luteinizing Hormone Surge.” J Endocr Soc 3(4): 716–733.
    1. Tsutsumi R and Webster NJ (2009). “GnRH pulsatility, the pituitary response and reproductive dysfunction.” Endocrine journal 56(6): 729–737.
    1. Van der Beek E, et al. (1994). “Preferential induction of c-fos immunoreactivity in vasoactive intestinal polypeptide-innervated gonadotropin-releasing hormone neurons during a steroid-induced luteinizing hormone surge in the female rat.” Endocrinology 134(6): 2636–2644.
    1. van der Beek EM, et al. (1997). “Evidence for a direct neuronal pathway from the suprachiasmatic nucleus to the gonadotropin-releasing hormone system: combined tracing and light and electron microscopic immunocytochemical studies.” J. Comp. Neurol 384(4): 569–579.
    1. Van Der Horst GT, et al. (1999). “Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms.” Nature 398(6728): 627.
    1. Vijayan E, et al. (1979). “Vasoactive intestinal peptide: evidence for a hypothalamic site of action to release growth hormone, luteinizing hormone, and prolactin in conscious ovariectomized rats.” Endocrinology 104(1): 53–57.
    1. Wang L, et al. (2019). “Genetic dissection of the different roles of hypothalamic kisspeptin neurons in regulating female reproduction.” eLife 8: e43999.
    1. Watson E, et al. (1995). “LH and progesterone concentrations during diestrus in the mare and the effect of hCG.” Theriogenology 43(8): 1325–1337.
    1. Welsh DK, et al. (1995). “Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms.” Neuron 14: 697–706.
    1. Welsh DK, et al. (2010). “Suprachiasmatic nucleus: cell autonomy and network properties.” Annu Rev Physiol 72: 551–577.
    1. Wiegand SJ and Terasawa E (1982). “Discrete lesions reveal functional heterogeneity of suprachiasmatic structures in regulation of gonadotropin secretion in the female rat.” Neuroendocrinology 34(6): 395–404.
    1. Wierman ME, et al. (2011). “Gonadotropin-releasing hormone (GnRH) neuron migration: initiation, maintenance and cessation as critical steps to ensure normal reproductive function.” Front. Neuroendocrinol 32(1): 43–52.
    1. Williams WP 3rd, et al. (2011). “Circadian control of kisspeptin and a gated GnRH response mediate the preovulatory luteinizing hormone surge.” Endocrinology 152(2): 595–606.
    1. Williams WP 3rd and Kriegsfeld LJ (2012). “Circadian control of neuroendocrine circuits regulating female reproductive function.” Frontiers in endocrinology 3: 60.
    1. Wintermantel TM, et al. (2006). “Definition of estrogen receptor pathway critical for estrogen positive feedback to gonadotropin-releasing hormone neurons and fertility.” Neuron 52(2): 271–280.
    1. Xu J, et al. (2016). “Loss of Bmal1 decreases oocyte fertilization, early embryo development and implantation potential in female mice.” Zygote 24(5): 760–767.
    1. Yoshikawa T, et al. (2009). “Timing of the ovarian circadian clock is regulated by gonadotropins.” Endocrinology 150(9): 4338–4347.
    1. Zhang Z, et al. (2017). “Rhythmic expression of circadian clock genes in the preovulatory ovarian follicles of the laying hen.” PLoS One 12(6): e0179019.
    1. Zhao S and Kriegsfeld LJ (2009). “Daily changes in GT1–7 cell sensitivity to GnRH secretagogues that trigger ovulation.” Neuroendocrinology 89(4): 448–457.

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