Relevant Scientific Citations for KynderMed

General articles on myometrium research

Smith R 2007 Parturition. N Engl J Med 356:271–283

  • A highly readable review of the current state of research into term and preterm human labor

Young WS, Shepard E, Amico J, et al. 1996 Deficiency in mouse oxytocin prevents milk ejection, but not fertility or parturition. J Neuroendocrinol. 8(11):847-853.

Nishimori K, Youn LJ, Guo Q, Wang Z, Insel TR, Matzuk MM 1996 Oxytocin is required for nursing but is not essential for parturition or reproductive behavior. Proc Natl Acad Sci U S A. 93(21): 11699-11704.

Takayanagi Y, Yoshida M, Bielsky IF, et al. 2005 Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. Proc Natl Acad Sci USA 102(44): 16096-16101.

  • The above three papers corroborate that oxytocin is not essential for labor in pregnant rodent models of parturition

Mendelson CR. 2009 Minireview: fetal-maternal hormonal signaling in pregnancy and labor. Mol Endocrinol 23(7):947-954.

  • An insightful examination of the controversies surrounding human parturition

Mitchell BF, Taggart MJ 2009 Are animal models relevant to key aspects of human parturition? Am J Physiol Regul Integr Comp Physiol. 297(3):R525-545.

  • These well-established researchers make a strong argument that the common non-primate models of parturition are not really suitable for clinical translation

Leake RD, Weitzman RE, Glatz TH, Fisher DA. 1981 Plasma oxytocin concentrations in men, nonpregnant women and pregnant women before and during spontaneous labor. J Clin Endocrinol Metab. 53(4):730-733.

Thornton S, Davison JM, Baylis PH. 1992 Plasma oxytocin during the first and second stages of spontaneous human labour. Acta Endocrinol. 126(5):425-429.

  • The above two papers show that maternal plasma oxytocin levels are low in pregnancy and only rising in some women after spontaneous labor is well underway

General reviews on melatonin physiology

Masana MI, Dubocovich ML 2001 Melatonin receptor signaling: finding the path through the dark. Sci STKE, PE39

Arendt J. 2006 Melatonin in humans: it’s about time. J Neuroendocrinol. 17(8):537-538.

Dubocovich ML, Delagrange P, Krause DN, Sugden D, Cardinali DP, Olcese J. 2010 International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol Rev. 62(3):343-380.

  • All three of the above review articles provide extensive information on the targets and actions of melatonin and its potential relevance for human health and disease

 Myometrium, Labor and Uterine Rhythms

Glattre E, Bjerkedal T. 1983 The 24-hour rhythmicity of birth: a population study. Acta Obstet Gynecol Scand. 62:31-36.

Cooperstock M, England JE, Wolfe RA. 1987 Circadian incidence of labor onset hour in preterm birth and chorioamnionitis. Obstet Gynecol. 70(6):852-855.

Zahn V, Hattensperger W 1993 Circadian rhythm of pregnancy contractions. Z Geburtshilfe Perinatol 197(1):1–10

Cagnacci A, Soldani R, Melis GB, Volpe A. 1998 Diurnal rhythms of labor and delivery in women: modulation by parity and seasons. Am J Obstet Gynecol. 178(1 pt 1):140-145.

Lindow SW, Jha RR, Thompson JW. 2000 24-hour rhythm to the onset of preterm labour. Br J Obstet Gynecol. 107(9): 1145-1148.

Vatish M, Steer PJ, Blanks AM, Hon M, Thornton S. 2010 Diurnal variation is lost in preterm deliveries before 28 weeks of gestation. Br J Obstet Gynecol. 117(6):765-767.

  • The above six papers confirm that uterine contractions in late term pregnancy as well as in term and preterm labor occurs primarily in the late night and early morning hours

Lincoln DW, Porter DG. 1976 Timing of the photoperiod and the hour of birth in rats. Nature. 260(5554): 780-781.

  • An early report on the presence of a circadian rhythm in the timing of birth in rodents

Reppert SM, Henshaw D, Schwartz WJ, Weaver DR. 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.

  • This seminal study demonstrated that ablation of the maternal circadian clock in pregnant rats perturbs the timing of birth, implicating a brain derived circadian signal for parturition

Harbert GM Jr. Biorhythms of the pregnant uterus (Macaca mulatta). Am J Obstet Gynecol. 1977; 129(4):401-408.

Morgan MA, Silavin SL, Wentworth RA, et al. Different patterns of myometrial activity and 24-h rhythms in myometrial contractility in the gravid baboon during the second half of pregnancy. Biol Reprod. 1992; 46(6):1158-116

Farber DM, Giussani DA, Jenkins SL, et al. 1997 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 56: 557–62.

  • The above three papers demonstrate that uterine contractions in the pregnant non-human primate also occur primarily in the late night and early morning hours

Melatonin, pregnancy and uterus

Kivela A, Kauppila A, Leppaluoto J, Vakkuri O 1989 Serum and amniotic fluid melatonin during human labor. J Clin Endocrinol Metab 69:1065–1068

Kivela A 1991 Serum melatonin during pregnancy. Acta Endocrinol (Copenh) 124: 233–237

  • The above two papers established that serum melatonin levels continued to peak at night during late pregnancy and during pregnancy irrespective of labor induction or cesarean delivery

Wierrani F, Grin W, Hlawaka B, Kroiss A, Gruenberger W. Elevated serum melatonin levels during human late pregnancy and labour. J Obstet Gynecol 1997; 17(5):449-451

  • This study determined that serum melatonin levels were elevated late in pregnancy and during labor

Schlabritz-Loutsevitch N, Hellner N, Middendorf R, Muller D, Olcese J 2003 The human myometrium as a target for melatonin. J Clin Endocrinol Metab 88(2): 908–913

 Sharkey J, Olcese J 2007 Transcriptional inhibition of oxytocin receptor expression in human myometrial cells by melatonin involves protein kinase C signaling. J Clin Endocrinol Metab 92:4015–4019

  • The above two early reports showed convincingly that the human myometrium is a target for melatonin via the expression of both known forms of melatonin receptors

Martensson LG, Andersson RG, Berg G 1996 Melatonin together with noradrenaline augments contractions of human myometrium. Eur J Pharmacol 316:273–275

  • This study showed that melatonin synergizes with alpha-adrenergic receptor activation to promote human myometrial contractility in vitro

Takayama H, Nakamura Y, Tamura H, et al.. 2003. Pineal gland (melatonin) affects the parturition time, but not luteal function and fetal growth, in pregnant rats. Endocrine J. 50(1):37-43.

  • This group determined that removal of the pineal gland (the source of melatonin) in pregnant rats disrupted the circadian timing of birth, and that properly timed hormone replacement restored this

Sharkey JT, Puttaramu R, Word RA, Olcese J. 2009 Melatonin synergizes with oxytocin to enhance contractility of human myometrial smooth muscle cells. J Clin Endocrinol Metab. 94(2):421-427.

  • A pioneering study that reveals numerous mechanisms through which melatonin activates human uterine contractions in vitro

 Hertz-Eshel M, Rahamimoff R. 1965 Effect of melatonin on uterine contractility. Life Sci. 4(14):1367-1372.

Burns JK. 1972 Effects of melatonin on some blood constituents and on uterine contractility in the rat. J Physiol 226(2):106P-107P.

  • The above two early reports were among the first to demonstrate an inhibitory effect of melatonin of uterine contractions in the nocturnally active pregnant rat

Steffens F, Zhou X-B, Sausbier U, et al. 2003 Melatonin receptor signaling in pregnant and nonpregnant rat uterine myocytes as probed by BKCa channel activity. Mol Endocrinol. 17(10): 2103-2115.

  • These authors identified significant differences in the signaling pathways used by the melatonin receptors in the myometrium of pregnant and nonpregant rats

Sharkey J, Cable C, Olcese J. 2010 Melatonin sensitizes human myometrial cells to oxytocin in a PKCα/ERK-dependent manner. J Clin Endocrinol Metab. 95(6):2902-2908.

  • The results here demonstrate that melatonin synergizes with oxytocin at numerous intracellular levels to activate pro-contractile events in human myometrial cells

Melatonin and light

Ducsay CA, Yellon SM. 1991 Photoperiod regulation of uterine activity and melatonin rhythms in the pregnant rhesus macaque. Biol Reprod. 44(6):967-974.

  • These authors demonstrated that the timing of birth in nonhuman primates can be phase-shifted by reversal of the light-dark cycles, implying circadian clock control of this event.

Lewy AJ, Wehr TA, Goodwin FK, Newsome DA, Markey SP. 1980 Light suppresses melatonin secretion in humans. Science 210(4475):1267-1269.

  • This seminal report showed that melatonin secretion is inhibited by white light

West KE, Jablonski MR, Warfield B, et al. 2011 Blue light from light-emitting diodes elicits a dose-dependent suppression of melatonin in humans. J Appl Physiol 110(3):619-626.

  • One of the first human trials demonstrating that blue light (469 nm) is effective in reducing human melatonin secretion

Figueiro MG, Bierman A, Rea MS. 2013 A train of blue light pulses delivered through closed eyelids suppresses melatonin and phase shifts the human circadian system. Nat Sci Sleep 5:133–41.

  • These results demonstrated that blue light (470 nm) penetrates the closed eyelids to significantly suppress melatonin levels in nonpregnant human subjects

Olcese J, Lozier S, Paradise C. 2013 Melatonin and the circadian timing of human

parturition. Reprod Sci 20:168–74.

Olcese J and S. Beesley 2014 Clinical significance of melatonin receptors in the human myometrium. Fert. Steril. 102: 329-335.

  • The data from the above two papers confirm that white light suppresses nocturnal melatonin secretion and uterine contractions in late term pregnant women

Brainard GC, Hanifin JP, Warfield B, et al. 2015 Short-wavelength enrichment of polychromatic light enhances human melatonin suppression potency. J Pineal Res. 58(3): 352-61

  • These authors showed that white light enriched with blue light (~450 nm) is more potent for suppressing human melatonin levels