Melatonin’s Role in Human Reproduction: Recent Studies

  • Rahimah ZakariaEmail author
  • Amnon Brzezinski
  • Venkataramanujam Srinivasan


Melatonin, N-acetyl-5-methhoxytryptamine, is a molecule with diverse physiological function. It affects reproductive functions in a wide variety of species. This chapter describes the roles of melatonin on various reproductive parameters. Melatonin has an inhibitory influence on hypothalamic GnRH secretion. Melatonin acts as antioxidant and reduces oxidative stress-induced testicular dysfunctions and poor oocytes quality in many experimental animals. During fetal life, melatonin regulates circadian rhythm and has been suggested to play a role in the regulation of fetal REM and NREM sleep. In adults, melatonin regulates the time of parturition in both humans and nonhuman primates. Many studies have suggested that melatonin could be an effective treatment for preeclampsia, due to its antioxidant properties as well as its antihypertensive and anticonvulsive actions.


Melatonin GnRH Parturition Oocyte Testes Preeclampsia 


  1. 1.
    Huebner O. Tumor des Glandula pinealis. Dtsch Med Wochenschr. 1898;24(pt 2):214–5.Google Scholar
  2. 2.
    Kitay JI, Altschule MD. The pineal gland. Cambridge: Harvard University Press; 1954.Google Scholar
  3. 3.
    Thieblot L, Le Bars H. Le Glande Pineale ou Epiphyse. Paris: Maloine; 1955.Google Scholar
  4. 4.
    Wurtman RJ, Axelrod J, Chu EW. Melatonin, a pineal substance: its effect on the rat ovary. Science. 1963;141:277–80.PubMedGoogle Scholar
  5. 5.
    Reiter RJ. The melatonin rhythm. Both a clock and calendar. Experientia. 1993;49:654–64.PubMedGoogle Scholar
  6. 6.
    Johnston JD, Messager S, Barrett P, Hazlerigg DG. Melatonin action in the pituitary: neuroendocrine synchronizer and developmental modulator? J Neuroendocrinol. 2003;15:405–8.PubMedGoogle Scholar
  7. 7.
    Rojansky N, Brzezinski A, Schenker JG. Seasonality in human reproduction: an update. Hum Reprod. 1992;7:735–45.PubMedGoogle Scholar
  8. 8.
    Kaupipila A, Kivela A, Pakarinen A, Vakkuri O. Inversed seasonal relationship between melatonin and ovarian activity in humans in a region with a strong seasonal contrast in luminosity. J Clin Endocrinol Metab. 1987;65:823–8.Google Scholar
  9. 9.
    Sanhal B. Seasonal birth pattern in Sweden in relation to birth order and maternal age. Acta Obstet Gynecol Scand. 1978;57:393–7.Google Scholar
  10. 10.
    Brzezinski A, Wurtman RJ. The pineal gland: it’s possible role in human reproduction. Obstet Gynecol Surv. 1988;43:197–207.PubMedGoogle Scholar
  11. 11.
    Brzezinski A. Melatonin in humans. N Engl J Med. 1997;336:186–95.PubMedGoogle Scholar
  12. 12.
    Sizonenko PC. Physiology of puberty. J Endocrinol Invest. 1989;12:59–63.PubMedGoogle Scholar
  13. 13.
    Waldhauser F, Steger H. Changes in melatonin secretion with age and pubescence. J Neural Transm. 1986;21(Suppl):183–97.Google Scholar
  14. 14.
    Waldhauser F, Weiszenbacher G, Tatzer E, Gisinger B, Waldhauser M, Schemper M, Frisch H. Alterations in nocturnal serum melatonin levels in humans with growth and aging. J Clin Endocrinol Metabol. 1988;66(3):648–52.Google Scholar
  15. 15.
    Iguchi H, Kato K, Ibayashi H. Age-dependent reduction in serum melatonin concentrations in healthy human subjects. J Clin Endocrinol Metabol. 1982;55:27–9.Google Scholar
  16. 16.
    Sack RL, Lewy AJ, Erb DL, Vollmer WM, Singer CM. Human melatonin production decreases with age. J Pineal Res. 1986;3:379–88.PubMedGoogle Scholar
  17. 17.
    Zhao ZY, Xie Y, Fu YR, Bogdan A, Touitou Y. Aging and the circadian rhythm of melatonin: a cross-sectional study of Chinese subjects 30–110 yr of age. Chronobiol Int. 2002;19:1171–82.PubMedGoogle Scholar
  18. 18.
    Carlomagno G, Nordio M, Chiu TT, Unfer V. Contribution of myo-inositol and melatonin to human reproduction. Eur J Obstet Gynecol Reprod Biol. 2011;159:267–72.PubMedGoogle Scholar
  19. 19.
    Buchanan KL, Yellon SM. Delayed puberty in the male Djungarian hamster: effect of short photoperiod or melatonin treatment on the Gn-RH neuronal system. Neuroendocrinology. 1991;54:96–102.PubMedGoogle Scholar
  20. 20.
    Silman RE. Melatonin and the human gonadotrophin-releasing hormone pulse generator. J Endocrinol. 1991;128:7–11.PubMedGoogle Scholar
  21. 21.
    Cavallo A. Melatonin and human puberty: current perspectives. J Pineal Res. 1993;15(3):115–21.PubMedGoogle Scholar
  22. 22.
    Crowley SJ, Acebo C, Carskadon MA. Human puberty: salivary melatonin profiles in constant conditions. Dev Psychobiol. 2012;54(4):468–73.PubMedGoogle Scholar
  23. 23.
    Cavallo A. Plasma melatonin rhythm in normal puberty: interactions of age and pubertal stages. Neuroendocrinology. 1992;55(4):372–9.PubMedGoogle Scholar
  24. 24.
    Waldhauser F, Boepple PA, Schemper M, Mansfield MJ, Crowley Jr WF. Serum melatonin in central precocious puberty is lower than in age-matched prepubertal children. J Clin Endocrinol Metabol. 1991;73(4):793–6.Google Scholar
  25. 25.
    Young IM, Francis PL, Leone AM, Stovell P, Silman RE. Constant pineal output and increasing body mass account for declining melatonin levels during human growth and sexual maturation. J Pineal Res. 1988;5(1):71–85.PubMedGoogle Scholar
  26. 26.
    Cavallo A, Dolan LM. 6-Hydroxymelatonin sulfate excretion in human puberty. J Pineal Res. 1996;21(4):225–30.PubMedGoogle Scholar
  27. 27.
    Fideleff HL, Boquete H, Fideleff G, Albornoz L, Lloret SP, Suarez M, Cardinali DP. Gender-related differences in urinary 6-sulfatoxymelatonin levels in obese pubertal individuals. J Pineal Res. 2006;40(3):214–8.PubMedGoogle Scholar
  28. 28.
    Salti R, Galluzzi F, Bindi G, Perfetto F, Tarquini R, Halberg F, Cornelissen G. Nocturnal melatonin patterns in children. J Clin Endocrinol Metabol. 2000;85:2137–44.Google Scholar
  29. 29.
    Cain SW, Dennison CF, Zeitzer JM, Guzik AM, Khalsa SB, Santhi N, Duffy JF. Sex differences in phase angle of entrainment and melatonin amplitude in humans. J Biol Rhythms. 2010;25(4):288–96.PubMedCentralPubMedGoogle Scholar
  30. 30.
    Wetterberg L, Bratlid T, von Knorring L, Eberhard G, Yuwiler A. A multinational study of the relationships between nighttime urinary melatonin production, age, gender, body size, and latitude. Eur Arch Psychiatry Clin Neurosci. 1999;249:256–62.PubMedGoogle Scholar
  31. 31.
    Burgess HJ, Fogg LF. Individual differences in the amount and timing of salivary melatonin secretion. PLoS One. 2008;3(8):e3055.PubMedCentralPubMedGoogle Scholar
  32. 32.
    Griefahn B, Brode P, Blaszkewicz M, Remer T. Melatonin production during childhood and adolescence: a longitudinal study on the excretion of urinary 6-hydroxymelatonin sulfate. J Pineal Res. 2003;34(1):26–31.PubMedGoogle Scholar
  33. 33.
    Penny R. Melatonin excretion in normal males and females: increase during puberty. Metabolism. 1982;31:816–23.PubMedGoogle Scholar
  34. 34.
    Waldhauser F, Weiszenbacher G, Frisch H, Zeitlhuber U, Waldhauser M, Wurtman RJ. Fall in nocturnal serum melatonin during prepuberty and pubescence. Lancet. 1984;1(8373):362–5.PubMedGoogle Scholar
  35. 35.
    Tsutsui K. A new key neurohormone controlling reproduction, gonadotropin-inhibitory hormone (GnIH): biosynthesis, mode of action and functional significance. Prog Neurobiol. 2009;88(1):76–88.PubMedGoogle Scholar
  36. 36.
    Ubuka T, Bentley GE, Ukena K, Wingfield JC, Tsutsui K. Melatonin induces the expression of gonadotropin-inhibitory hormone in the avian brain. Proc Natl Acad Sci U S A. 2005;102(8):3052–7.PubMedCentralPubMedGoogle Scholar
  37. 37.
    Cohen HN, Hay ID, Anneswley TM, Beastall GH, Wallace AM, Spooner R, Thomson JA, Eastwold P, Klee GG. Serum immunoreactive melatonin in boys with delayed puberty. Clin Endocrinol. 1982;17:291–7.Google Scholar
  38. 38.
    Commentz JC, Helmke K. Precocious puberty and decreased melatonin secretion due to a hypothalamic hamartoma. Horm Res. 1995;44(6):271–5.PubMedGoogle Scholar
  39. 39.
    Cavallo A. Plasma melatonin rhythm in disorders of puberty: interactions of age and pubertal stages. Horm Res. 1991;36(1–2):16–21.PubMedGoogle Scholar
  40. 40.
    Ehrenkranz JR, Tamarkin L, Comite F, Johnsonbaugh RE, Bybee DE, Loriaux DL, Cutler Jr GB. Daily rhythm of plasma melatonin in normal and precocious puberty. J Clin Endocrinol Metabol. 1982;55(2):307–10.Google Scholar
  41. 41.
    Berga SL, Jones KL, Kaufmann S, Yen SS. Nocturnal melatonin levels are unaltered by ovarian suppression in girls with central precocious puberty. Fertil Steril. 1989;52(6):936–41.PubMedGoogle Scholar
  42. 42.
    Silman RE, Leone RM, Hooper RJ, Preece MA. Melatonin, the pineal gland and human puberty. Nature. 1979;282(5736):301–3.PubMedGoogle Scholar
  43. 43.
    Arendt J. Melatonin and the mammalian pineal gland. 1st ed. London: Chapman & Hall; 1995. p. 17.Google Scholar
  44. 44.
    Brzezinski A. Melatonin and human reproduction: why the effect is so elusive? In: Pandi-Perumal SR, Cardinali Melatonin DP, editors. From molecules to therapy. New York: Nova; 2007. p. 219–25.Google Scholar
  45. 45.
    Brzezinski A, Lynch HJ, Wurtman RJ, Seibel MM. Possible contribution of melatonin to the timing of the luteinizing hormone surge. N Engl J Med. 1987;316:1550–1.PubMedGoogle Scholar
  46. 46.
    Laughin GA, Loucks AB, Yen SCC. Marked augmentation of nocturnal melatonin secretion in amenorrheic athletes but not in cycling atheletes. Unaltered by opiodergic or dopaminergic blockade. J Clin Endocrinol Metab. 1991;73:1321–6.Google Scholar
  47. 47.
    Aleandri V, Spina V, Morini A. The pineal gland and reproduction. Hum Reprod Update. 1996;3:225–35.Google Scholar
  48. 48.
    Roy D, Belsham DD. Melatonin receptor activation regulates GnRH gene expression and secretion in GT1-7Gn-RH neurons. Signal transduction mechanisms. J Biol Chem. 2002;277:251–8.PubMedGoogle Scholar
  49. 49.
    Brzezinski A, Siebel MM, Lynch HJ, Deng MH, Wurtman RJ. Melatonin in human preovulatory follicular fluid. J Clin Endocrinol Metab. 1987;64:865–7.PubMedGoogle Scholar
  50. 50.
    Ronnberg L, Kauppila A, Leppaluoto J, Marikainen H, Vakkuuri O. Circadian and seasonal variation in human preovulatory follicular fluid melatonin concentration. J Clin Endocrinol Metab. 1990;71:492–6.PubMedGoogle Scholar
  51. 51.
    Ayre EA, Wang ZP, Brown GM, Pang SF. Localization and characterization of [125I] iodomelatonin binding sites in duck gonads. J Pineal Res. 1994;17:39–47.PubMedGoogle Scholar
  52. 52.
    Ayre EA, Pang SF. 2-[125I] Iodomelatonin binding sites in the testis and ovaries: putatitive melatonin receptors in the gonads. Biol Signals. 1994;3:71–84.PubMedGoogle Scholar
  53. 53.
    Cagnacci A, Volpe A. Influence of melatonin and photoperiod on animal and human reproduction. J Endocrinol Invest. 1996;19:382–411.PubMedGoogle Scholar
  54. 54.
    Yu ZH, Chow PH, Pang SF. Identification and characterization of 2[125I]-iodomelatonin binding sites in the rat epididymis. J Pineal Res. 1994;17:195–201.PubMedGoogle Scholar
  55. 55.
    Ng TB, Lo L. Inhibitory actions of pineal indoles on steroidogenesis in isolated rat Leydig cells. J Pineal Res. 1988;5:229–43.PubMedGoogle Scholar
  56. 56.
    Persengiev S, Kehajova J. Inhibitory actions of melatonin and structurally related compounds on testosterone production by mouse leydig cells in vitro. Cell Biochem Funct. 1991;9:281–6.PubMedGoogle Scholar
  57. 57.
    Shiu SYW, Yu ZH, Chow PH, Pang SF. Putative melatonin receptors in the male reproductive tissues. Front Horm Res. 1996;21:90–100.Google Scholar
  58. 58.
    Shiu SYW, Li L, Wong JTY, Pang SF. Biology of G-protein coupled melatonin receptors in the epididymis and prostate of mammals. Chin Med J. 1997;110:648–55.PubMedGoogle Scholar
  59. 59.
    Laudon M, Gilad E, Matzkin H, Braf Z, Zisapel N. Putatitive melatonin receptors in benign prostate tissue. J Clin Endocrinol Metab. 1996;81:1336–42.PubMedGoogle Scholar
  60. 60.
    Gilad E, Laudon M, Matzkin H, Pick E, Sofer M, Braf Z, Zisapel N. Functional melatonin receptors in the human prostate epithelial cells. Endocrinology. 1996;137:1412–7.PubMedGoogle Scholar
  61. 61.
    Awad H, Halawa F, Mostafa T, Atta H. Melatonin hormone profile in infertile males. Int J Androl. 2006;29:409–13.PubMedGoogle Scholar
  62. 62.
    Semercioz A, Onur R, Ogras S, Orhan I. Effects of melatonin on testicular tissue nitric oxide level and antioxidant enzyme activities in experimentally induced left varicocele. Neuro Endocrinol Lett. 2003;24:86–90.PubMedGoogle Scholar
  63. 63.
    Guneli E, Tugyan K, Ozturk H, Gumustekin M, Cilaker S, Uysal N. Effect of melatonin on testicular damage in streptozotocin-induced diabetes rats. Eur Surg Res. 2008;40:354–60.PubMedGoogle Scholar
  64. 64.
    Zhang K, Lv Z, Jia X, Huang D. Melatonin prevents testicular damage in hyperlipidaemic mice. Andrologia. 2012;44:230–6.PubMedGoogle Scholar
  65. 65.
    Koksal M, Oğuz E, Baba F, Ali Eren M, Ciftci H, Demir ME, Kurcer Z, Take G, Aral F, Ocak AR, Aksoy N, Ulas T. Effects of melatonin on testis histology, oxidative stress and spermatogenesis after experimental testis ischemia-reperfusion in rats. Eur Rev Med Pharmacol Sci. 2012;16:582–8.PubMedGoogle Scholar
  66. 66.
    Rao MV, Bhatt RN. Protective effect of melatonin on fluoride-induced oxidative stress and testicular dysfunction in rats. Res Rep Fluoride. 2012;45(2):116–24.Google Scholar
  67. 67.
    du Plessis SS, Hagenaar K, Lampiao F. The in vitro effects of melatonin on human sperm function and its scavenging activities on NO and ROS. Andrologia. 2010;42:112–6.PubMedGoogle Scholar
  68. 68.
    Bornman MS, Oosthuizen JM, Barnard HC, Schulenburg GW, Boomker D, Reif S. Melatonin and sperm motility. Andrologia. 1989;21:483–5.PubMedGoogle Scholar
  69. 69.
    van Vuuren RJ, Pitout MJ, van Aswegen CH, Theron JJ. Putative melatonin receptor in human spermatozoa. Clin Biochem. 1992;25:125–7.PubMedGoogle Scholar
  70. 70.
    Fujinoki M. Melatonin-enhanced hyperactivation of hamster sperm. Reproduction. 2008;136:533–41.PubMedGoogle Scholar
  71. 71.
    Puolakka J, Jarvinen PA, Kauppila A. Changing pattern of childbirth in northern Finland over the past three decades. In: Fortune circumpolar health. Seattle and London: University of Washington Press; 1985. p. 181–5.Google Scholar
  72. 72.
    Kauppilla A, Kivela A, Pakarinen A, Vakkuri O. Inverse seasonal relationship between melatonin and ovarian activity in humans in a region with a strong seasonal contrast in luminosity. J Clin Endocrinol Metab. 1987;65:823–8.Google Scholar
  73. 73.
    Kivela A, Kauppila A, Ylostalo P, Vakkuri O. Seasonal, menstrual and circadian secretion of melatonin gonadotrophins and prolactin in women. Acta Physiol Scand. 1988;132:321–7.PubMedGoogle Scholar
  74. 74.
    Reiter RJ, Tan DX, Fuentes-Broto L. Melatonin: a multitasking molecule. Prog Brain Res. 2010;181:127–51.PubMedGoogle Scholar
  75. 75.
    Tamura H, Takasaki A, Miwa I, et al. Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate. J Pineal Res. 2008;44:280–7.PubMedGoogle Scholar
  76. 76.
    Nakamura Y, Tamura H, Kashida S, Takayama H, Yagamata Y, Karube A, Sugino N, Kato H. Changes of serum melatonin level and its relationship to feto-placental unit during pregnancy. J Pineal Res. 2001;30:29–33.PubMedGoogle Scholar
  77. 77.
    Kivela A. Serum melatonin during human pregnancy. Acta Endocrinol (Copenh). 1991;124:233–7.Google Scholar
  78. 78.
    Yellon SM, Longo LD. Effect of maternal pinealectomy and reverse photoperiod n the circadian melatonin in the sheep and fetus during the last trimester of pregnancy. Biol Reprod. 1988;39:1093–9.PubMedGoogle Scholar
  79. 79.
    Munoz-Hoyos A, Jaldo-Alba F, Molina-Carballo A, Rodriguez-Cabezas T, Molina-Font JA, Acuna-Castroviejo D. Absence of plasma melatonin circadian rhythm during the first 72 h of life in human infants. J Clin Endocrinol Metab. 1993;77:699–703.PubMedGoogle Scholar
  80. 80.
    Reppert SM, Weaver DR, Rivkees SA, Stopa EC. Putative melatonin receptor in a human biological clock. Science. 1998;242:78–81.Google Scholar
  81. 81.
    Thomas I, Pervis CC, Drew JE, Abramovich DR, Williams LM. Melatonin receptors in human fetal brain: 2-[125I] iodomelatonin binding site and MT1 gene expression. J Pineal Res. 2002;33:218–24.PubMedGoogle Scholar
  82. 82.
    Hawkins GA, Meyers DA, Bleeker ER, Pack AI. Identification of coding polymorphisms in human circadian rhythm genes Per 1, Per2, Per3, clock, AmtI, Cry1, Cry2, and timeless in multiethnic screening panel. DNA Seq. 2007;10:1.Google Scholar
  83. 83.
    Okatani Y, Okamura K, Hayashi K, Wakatsuki A, Tamura S, Sagara Y. Maternal-fetal transfer of melatonin in pregnant women near term. J Pineal Res. 1998;25:129–34.PubMedGoogle Scholar
  84. 84.
    Mirmiran M, Maas YG, Ariagno RL. Development of fetal and neonatal sleep and circadian rhythms. Sleep Med Rev. 2003;7:321–34.PubMedGoogle Scholar
  85. 85.
    Fait V, Sela S, Ophir E, Khoury S, Nissimov J, Tkach M, Hirsch Y, Khotaba S, Tarasowa L, Oettinger M. Hyperemesis gravidarum is associated with oxidative stress. Am J Perinatol. 2002;19:93–8.PubMedGoogle Scholar
  86. 86.
    Myatt L, Cui X. Oxidative stress in placenta. Histochem Cell Biol. 2004;122:369–82.PubMedGoogle Scholar
  87. 87.
    Reiter RJ. Interaction of the pineal hormone melatonin with oxygen centered free radicals: a brief review. Braz J Med Biol Res. 2003;26:1141–55.Google Scholar
  88. 88.
    Srinivasan V. Melatonin, oxidative stress and neurodegenerative diseases. Indian J Expt Biol. 2002;40:668–79.Google Scholar
  89. 89.
    Srinivasan V, Pandi-Perumal SR, Maestroni GJ, Esquifino AJ, Hardeland R, Cardinali DP. Role of melatonin in neurodegenerative diseases. Neurotox Res. 2005;7:293–318.PubMedGoogle Scholar
  90. 90.
    Tamura H, Nakamura Y, Terron MP, Flores LJ, Manchester LC, Tan DX, Sugino N, Reiter RJ. Melatonin and pregnancy in the human. Reprod Toxicol. 2008;25:291–303.PubMedGoogle Scholar
  91. 91.
    Wakatsuki A, Okatani Y, Ikenouse N, Shinohara K, Watanabe K, Fukaya T. Melatonin protects against oxidized low density lipoprotein induced inhibition of nitric oxide production in human umbilical artery. J Pineal Res. 2001;31:281–8.PubMedGoogle Scholar
  92. 92.
    Milczarek R, Klimek J, Zelewski L. Melatonin inhibits NADPH-dependent lipid peroxidation in human placental mitochondria. Horm Metab Res. 2000;32:84–5.PubMedGoogle Scholar
  93. 93.
    Simko F, Paulis L. Melatonin as a potential antihypertensive treatment. J Pineal Res. 2007;42:319–22.PubMedGoogle Scholar
  94. 94.
    Pagni CA, Zenga F. Posttraumatic epilepsy with special emphasis on prophylaxis and prevention. Acta Neurochir Suppl. 2005;93:27–34.PubMedGoogle Scholar
  95. 95.
    Plaut SM, Grota LJ, Ader R, Graham CW. Effects of handling and the light–dark cycle on time of parturition in the rat. Lab Anim Care. 1970;20:447–53.PubMedGoogle Scholar
  96. 96.
    Boer K, Lincoln DW, Swaab DF. Effects of electrical stimulation of the neurohypophysis on labour in the rat. J Endocrinol. 1975;65:163–76.PubMedGoogle Scholar
  97. 97.
    Lincoln DW, Porter DG. Timing of the photoperiod and the hour of birth in rats. Nature. 1976;260:780–1.PubMedGoogle Scholar
  98. 98.
    Takayama H, Nakamura Y, Tamura H, Yamaagata Y, Harada A, Nakata M, Sugino N, Kato H. Pineal gland (melatonin) affects the parturition time, but not luteal function and fetal growth, in pregnant rats. Endocr J. 2003;50:37–43.PubMedGoogle Scholar
  99. 99.
    Glattre E, Bjerkedal T. The 24-hour rhythmicity of birth: a population study. Acta Obstet Gynecol Scand. 1983;62:31–6.PubMedGoogle Scholar
  100. 100.
    Cooperstock M, England JE, Wolfe RA. Circadian incidence of labor onset hour in preterm birth and chorioamnionitis. Obstet Gynecol. 1987;70:852–5.PubMedGoogle Scholar
  101. 101.
    Lindow SW, Jha RR, Thompson JW. 24-hour rhythm to the onset of preterm labour. BJOG. 2000;107:1145–8.PubMedGoogle Scholar
  102. 102.
    Vatish M, Steer PJ, Blanks AM, Hon M, Thornton S. Diurnal variation is lost in preterm deliveries before 28 weeks of gestation. BJOG. 2010;117:765–7.PubMedGoogle Scholar
  103. 103.
    Longo LD, Yellon SM. Biological time keeping during pregnancy and the role of circadian rhythms during parturition. In: Kunzel W, Jensen A, editors. The endocrine control of the fetus. Berlin: Springer; 1988. p. 173–92.Google Scholar
  104. 104.
    Schlabritz-Loutsevitch N, Hellner N, Middendorf R, Muller D, Olcese J. The human myometrium as a target for melatonin. J Clin Endocrinol Metab. 2003;88:908–13.PubMedGoogle Scholar
  105. 105.
    Martensson LG, Andersson RG, Berg G. Melatonin together with noradrenaline augments contractions of human myometrium. Eur J Pharmacol. 1996;316:273–5.PubMedGoogle Scholar
  106. 106.
    Salomonis N, Cotte N, Zambon AC, Pollard KS, Vranizan K, Doniger SW, Dolganov G, Conklin BR. Identifying genetic networks underlying myometrial transition to labor. Genome Biol. 2005;6:R12.1–R16.Google Scholar
  107. 107.
    Olecese J. Melatonin effects on uterine physiology. In: Pandi-Perumal SR, Cardinali DP, editors. Melatonin: from molecules to therapy. New York: Nova; 2007. p. 205–25.Google Scholar
  108. 108.
    Ducsay CA, Yellon SM. Photoperiod regulation of uterine activity and melatonin rhythms in the pregnant rhesus macaque. Biol Reprod. 1991;44:967–74.PubMedGoogle Scholar
  109. 109.
    Zahn V, Hattensperger W. Circadian rhythm of pregnancy contractions. Z Geburtshilfe Perinatol. 1993;197:1–10.PubMedGoogle Scholar
  110. 110.
    Farber DM, Giussani DA, Jenkins SL, Mecenas CA, Winter JA, Wentworth RA, Nathanielsz PW. Timing of the switch from myometrial contractures to contractions in late-gestation pregnant rhesus monkeys as recorded by myometrial electromyogram during spontaneous term and androstenedione-induced labor. Biol Reprod. 1997;56:557–62.PubMedGoogle Scholar
  111. 111.
    Olcese J. Circadian aspects of mammalian parturition: a review. Mol Cell Endocrinol. 2012;349:62–7.PubMedGoogle Scholar
  112. 112.
    Reppert SM, Weaver DR. Coordination of circadian timing in mammals. Nature. 2002;418:935–41.PubMedGoogle Scholar
  113. 113.
    Sharkey JT, Puttaramu R, Word RA, Olcese J. Melatonin synergizes with oxytocin to enhance contractility of human myometrial smooth muscle cells. J Clin Endocrinol Metab. 2009;94:421–7.PubMedGoogle Scholar
  114. 114.
    Lerner AB, Case JD, Takahashi Y, Lee Y, Mori W. Isolation of melatonin, the pineal gland factor that lightens melanocytes. J Am Chem Soc. 1958;80:2587.Google Scholar
  115. 115.
    Stevens RG. Circadian disruption and breast cancer: from melatonin to clock genes. Epidemiology. 2005;16:254–8.PubMedGoogle Scholar

Copyright information

© Springer India 2014

Authors and Affiliations

  • Rahimah Zakaria
    • 1
    Email author
  • Amnon Brzezinski
    • 2
  • Venkataramanujam Srinivasan
    • 3
    • 4
    • 5
  1. 1.Department of PhysiologySchool of Medical Sciences, Universiti Sains MalaysiaKubang Kerian, KelantanMalaysia
  2. 2.Department of Obstetrics and GynecologyHadassah Hebrew-University Medical CenterJerusalemIsrael
  3. 3.Sri Sathya Sai Medical Educational and Research Foundation, An International Medical Sciences Research Study CenterCoimbatoreIndia
  4. 4.National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and TreatmentHospital “G. Mazzini”TeramoItaly
  5. 5.Department of Neuroscience and ImagingUniversity “G.D’ Annunzio”ChietiItaly

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