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Physiology of parturition

Errol R Norwitz, MD, PhD, MBA
Section Editor
Charles J Lockwood, MD, MHCM
Deputy Editor
Vanessa A Barss, MD, FACOG


Labor is a physiological event involving a sequential, integrated set of changes within the myometrium, decidua, and uterine cervix that occur gradually over a period of days to weeks. Biochemical connective tissue changes in the uterine cervix appear to precede uterine contractions and cervical dilation, and all of these events usually occur before rupture of the fetal membranes.

Labor is a clinical diagnosis, which includes (i) the presence of regular phasic uterine contractions increasing in frequency and intensity, and (ii) progressive cervical effacement and dilatation. A show (bloody discharge) may or may not be present. Cervical dilatation in the absence of uterine contractions is seen most commonly in the second trimester and is suggestive of cervical insufficiency (see "Cervical insufficiency"). Similarly, the presence of uterine contractions in the absence of cervical change does not meet criteria for the diagnosis of labor. Such contractions are often attributed to "false labor" or uterine irritability. The myometrial contractility pattern changes in labor from "contractures" (long-lasting, low frequency activity) to "contractions" (high intensity, high frequency activity) [1].

Labor and delivery are not passive processes by which uterine contractions push a rigid object through a fixed aperture. The ability of the fetus to successfully negotiate the pelvis during labor and delivery depends upon a complex interaction of three variables: power (uterine contractions), passenger (fetus), and passage (both bony pelvis and pelvic soft tissues). Although conventional wisdom dictates that powerful contractions are more likely to be associated with a successful outcome, there are no data to support this conclusion. Furthermore, precipitous labor probably results from low resistance of the pelvic soft tissues (the cervix in the first stage of labor and the muscles of the pelvic floor in the second stage) rather than from high myometrial activity [2].


The mean duration of human singleton pregnancy is 280 days (40 weeks) from the first day of the last menstrual period. A term pregnancy is defined as the period from 259 to 293 days after the first day of the last menstrual period (370/7ths to 416/7ths weeks).

Term labor may be regarded physiologically as a release from the inhibitory effects of pregnancy on the myometrium, rather than as an active process mediated by uterine stimulants. As an example, strips of myometrium obtained from a quiescent uterus at term and placed in an isotonic water bath will contract vigorously and spontaneously without added stimuli [3,4]. Nevertheless, both inhibitory and stimulatory mechanisms likely play a role in uterine activity.


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Literature review current through: Sep 2016. | This topic last updated: Jun 16, 2015.
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  1. Nathanielsz PW, Giussani DA, Wu WX. Stimulation of the switch in myometrial activity from contractures to contractions in the pregnant sheep and nonhuman primate. Equine Vet J Suppl 1997; :83.
  2. Norwitz, ER, Robinson JN, Repke, JT. Labor and Delivery. In: Obstetrics: Normal and Problem Pregnancies, 4th ed, Gabbe SG, Niebyl JR, Simpson JL (Eds), W.B. Saunders Company, New York 2001. p. 353.
  3. López Bernal A, Rivera J, Europe-Finner GN, et al. Parturition: activation of stimulatory pathways or loss of uterine quiescence? Adv Exp Med Biol 1995; 395:435.
  4. Garrioch DB. The effect of indomethacin on spontaneous activity in the isolated human myometrium and on the response to oxytocin and prostaglandin. Br J Obstet Gynaecol 1978; 85:47.
  5. MacDonald, PC. Parturition: Biomolecular and physiologic process. In: Williams Obstetrics, Cunningham FG, MacDonald, PC, Gant, NF, Leveno, KJ, Gilstrap, LC III (Eds), 19th ed, Appleton & Lange, Connecticut 1993. p. 298.
  6. Challis, JRG, Gibb, W. Control of parturition. Prenat Neonat Med 1996; 1:283.
  7. Norwitz ER, Robinson JN, Challis JR. The control of labor. N Engl J Med 1999; 341:660.
  8. Smith R. Parturition. N Engl J Med 2007; 356:271.
  9. Myers DA, Nathanielsz PW. Biologic basis of term and preterm labor. Clin Perinatol 1993; 20:9.
  10. Thorburn, GD, Challis, JRG, Robinson, JS. The endocrinology of parturition. In: Cellular Biology of the Uterus, Wynn, RM (Ed), Plenum Press, New York 1977. p. 653.
  11. Casey, LM, MacDonald, PC. The initiation of labour in women: Regulation of phospholipid and arachidonic acid metabolism and of prostaglandin production. In: Seminars in Perinatology, vol. 10, Creasy, RK, Warshaw, JB (Eds), Irvine & Stratton, Florida 1986. p. 270.
  12. Liggins, GC. The onset of labour: An overview. In: The onset of labour: Cellular and integrative mechanisms. A National Institute of Child Health and Human Development Research Planning Workshop (November 29-December 1, 1987), McNellis, D, Challis, JRG, MacDonald, PC, Nathanielsz, PW, Roberts, JM (Eds), Perinatology Press, Ithaca, New York 1988. p. 1.
  13. Huber A, Hudelist G, Czerwenka K, et al. Gene expression profiling of cervical tissue during physiological cervical effacement. Obstet Gynecol 2005; 105:91.
  14. Duff P, Huff RW, Gibbs RS. Management of premature rupture of membranes and unfavorable cervix in term pregnancy. Obstet Gynecol 1984; 63:697.
  15. Norwitz, ER, Robinson, JN, Repke, JT. The initiation of parturition: A comparative analysis across the species. Current Problems Obstet Gynecol Fertil 1999; 22:41.
  16. Liggins GC, Fairclough RJ, Grieves SA, et al. The mechanism of initiation of parturition in the ewe. Recent Prog Horm Res 1973; 29:111.
  17. Flint, APF, Anderson, ABM, Steele, PA, et al. The mechanism by which fetal cortisol controls the onset of parturition in the sheep. Biochem Soc Trans 1975; 3:1189.
  18. Matthews SG, Challis JR. Regulation of the hypothalamo-pituitary-adrenocortical axis in fetal sheep. Trends Endocrinol Metab 1996; 7:239.
  19. Liggins GC. Initiation of labour. Biol Neonate 1989; 55:366.
  20. Cinque B, Navarretta V, Benedetto MT, et al. Labor in humans: 1. Progesterone, 20 alpha-dihydro-progesterone, estrone and 17 beta-estradiol in near placental and most distant human amnion and chorion laeve in various stages of labor at term. J Endocrinol Invest 1986; 9:487.
  21. Garfield RE, Blennerhassett MG, Miller SM. Control of myometrial contractility: role and regulation of gap junctions. Oxf Rev Reprod Biol 1988; 10:436.
  22. Phaneuf S, Europe-Finner GN, Varney M, et al. Oxytocin-stimulated phosphoinositide hydrolysis in human myometrial cells: involvement of pertussis toxin-sensitive and -insensitive G-proteins. J Endocrinol 1993; 136:497.
  23. Phaneuf S, Europe-Finner GN, Carrasco MP, et al. Oxytocin signalling in human myometrium. Adv Exp Med Biol 1995; 395:453.
  24. Europe-Finner GN, Phaneuf S, Watson SP, López Bernal A. Identification and expression of G-proteins in human myometrium: up-regulation of G alpha s in pregnancy. Endocrinology 1993; 132:2484.
  25. Europe-Finner GN, Phaneuf S, Tolkovsky AM, et al. Down-regulation of G alpha s in human myometrium in term and preterm labor: a mechanism for parturition. J Clin Endocrinol Metab 1994; 79:1835.
  26. Hurd WW, Gibbs SG, Ventolini G, et al. Shortening increases spontaneous contractility in myometrium from pregnant women at term. Am J Obstet Gynecol 2005; 192:1295.
  27. Terzidou V, Sooranna SR, Kim LU, et al. Mechanical stretch up-regulates the human oxytocin receptor in primary human uterine myocytes. J Clin Endocrinol Metab 2005; 90:237.
  28. Pauerstein CJ, Zauder HL. Autonomic innervation, sex steroids and uterine contractility. Obstet Gynecol Surv 1970; 25:Suppl:617.
  29. Keirse, MJNC. Endogenous prostaglandins in human parturition. In: Human Parturition. Keirse, MJNC, Anderson, ABM, Bennebroek-Gravenhorstm, J, (Eds), Leiden University Press, Leiden 1979. p. 101.
  30. Liggins, GC. Initiation of parturition. In: Fetal Endocrinology, Novy, MJ, Resko, JA, (Eds), Academic Press, New York 1981. p. 211.
  31. Keirse, MJNC, Turnbull, AC. Prostaglandins in amniotic fluid during late pregnancy and labour. J Obstet Gynaecol Br Commonw 1973: 80:970.
  32. Casey ML, MacDonald PC. Biomolecular processes in the initiation of parturition: decidual activation. Clin Obstet Gynecol 1988; 31:533.
  33. Romero R, Munoz H, Gomez R, et al. Increase in prostaglandin bioavailability precedes the onset of human parturition. Prostaglandins Leukot Essent Fatty Acids 1996; 54:187.
  34. Casey, LM, MacDonald, PC. The initiation of labour in women: Regulation of phospholipid and arachidonic acid metabolism and of prostaglandin production. In: Seminars in Perinatology, Creasy, RK, Warshaw, JB, (Eds), Irvine & Stratton, Florida 1986. p. 270.
  35. Karim SM, Hillier K. Prostaglandins in the control of animal and human reproduction. Br Med Bull 1979; 35:173.
  36. Zuckerman H, Reiss U, Rubinstein I. Inhibition of human premature labor by indomethacin. Obstet Gynecol 1974; 44:787.
  37. Wigvist N, Lundström V, Gréen K. Premature labor and indomethacin. Prostaglandins 1975; 10:515.
  38. Peyron R, Aubény E, Targosz V, et al. Early termination of pregnancy with mifepristone (RU 486) and the orally active prostaglandin misoprostol. N Engl J Med 1993; 328:1509.
  39. Spitz IM, Bardin CW. Mifepristone (RU 486)--a modulator of progestin and glucocorticoid action. N Engl J Med 1993; 329:404.
  40. Csapo AI, Pulkkinen MO, Wiest WG. Effects of luteectomy and progesterone replacement therapy in early pregnant patients. Am J Obstet Gynecol 1973; 115:759.
  41. Zakar T, Mesiano S. How does progesterone relax the uterus in pregnancy? N Engl J Med 2011; 364:972.
  42. Turnbull, AC. The endocrine control of labour. In: Obstetrics, Turnbull, AC, Chamberlain, G, (Eds), Churchill Livingston, London 1989. p. 189.
  43. Haluska GJ, Cook MJ, Novy MJ. Inhibition and augmentation of progesterone production during pregnancy: effects on parturition in rhesus monkeys. Am J Obstet Gynecol 1997; 176:682.
  44. Frydman R, Lelaidier C, Baton-Saint-Mleux C, et al. Labor induction in women at term with mifepristone (RU 486): a double-blind, randomized, placebo-controlled study. Obstet Gynecol 1992; 80:972.
  45. Elliott CL, Brennand JE, Calder AA. The effects of mifepristone on cervical ripening and labor induction in primigravidae. Obstet Gynecol 1998; 92:804.
  46. Parker CR Jr, Illingworth DR, Bissonnette J, Carr BR. Endocrine changes during pregnancy in a patient with homozygous familial hypobetalipoproteinemia. N Engl J Med 1986; 314:557.
  47. Zakar T, Hertelendy F. Progesterone withdrawal: key to parturition. Am J Obstet Gynecol 2007; 196:289.
  48. Novy MJ, Walsh SW. Dexamethasone and estradiol treatment in pregnant rhesus macaques: effects on gestational length, maternal plasma hormones, and fetal growth. Am J Obstet Gynecol 1983; 145:920.
  49. Garfield RE, Kannan MS, Daniel EE. Gap junction formation in myometrium: control by estrogens, progesterone, and prostaglandins. Am J Physiol 1980; 238:C81.
  50. Fuchs, AR. The role of oxytocin in parturition. In: The Physiology and Biochemistry of the Uterus in Pregnancy and Labour, Huszar, G, (Ed), CRC Press, Boca Raton, Florida 1986. p. 163.
  51. Germain, AM, Kato, S, Villarroel, LA, Valenzuela, GJ, Serón-Ferré, M. Human term and preterm delivery is preceded by a rise in maternal plasma 17*-estradiol. Prenat Neonat Med 1996; 1:57.
  52. Figueroa JP, Honnebier MB, Binienda Z, et al. Effect of a 48-hour intravenous delta 4-androstenedione infusion on the pregnant rhesus monkey in the last third of gestation: changes in maternal plasma estradiol concentrations and myometrial contractility. Am J Obstet Gynecol 1989; 161:481.
  53. Giussani DA, Jenkins SL, Mecenas CA, et al. Daily and hourly temporal association between delta4-androstenedione-induced preterm myometrial contractions and maternal plasma estradiol and oxytocin concentrations in the 0.8 gestation rhesus monkey. Am J Obstet Gynecol 1996; 174:1050.
  54. Mecenas CA, Giussani DA, Owiny JR, et al. Production of premature delivery in pregnant rhesus monkeys by androstenedione infusion. Nat Med 1996; 2:443.
  55. Zeeman GG, Khan-Dawood FS, Dawood MY. Oxytocin and its receptor in pregnancy and parturition: current concepts and clinical implications. Obstet Gynecol 1997; 89:873.
  56. Fuchs AR, Fuchs F. Endocrinology of human parturition: a review. Br J Obstet Gynaecol 1984; 91:948.
  57. Nathanielsz PW, Honnebier MB, Mecenas C, et al. Effect of the oxytocin antagonist atosiban (1-deamino-2-D-tyr(OET)-4-thr-8-orn-vasotocin/oxytocin) on nocturanl myometrial contractions, maternal cardiovascular function, transplacental passage, and fetal oxygenation in the pregnant baboon during the last third of gestation. Biol Reprod 1997; 57:320.
  58. Fuchs AR, Fuchs F, Husslein P, et al. Oxytocin receptors and human parturition: a dual role for oxytocin in the initiation of labor. Science 1982; 215:1396.
  59. Fuchs AR, Fuchs F, Husslein P, Soloff MS. Oxytocin receptors in the human uterus during pregnancy and parturition. Am J Obstet Gynecol 1984; 150:734.
  60. Dawood MY, Wang CF, Gupta R, Fuchs F. Fetal contribution to oxytocin in human labor. Obstet Gynecol 1978; 52:205.
  61. Ferguson, JKW. A study of the motility of the intact uterus at term. Surg Gynecol Obstet 1941; 73:359.
  62. Campbell EA, Linton EA, Wolfe CD, et al. Plasma corticotropin-releasing hormone concentrations during pregnancy and parturition. J Clin Endocrinol Metab 1987; 64:1054.
  63. Sasaki A, Shinkawa O, Margioris AN, et al. Immunoreactive corticotropin-releasing hormone in human plasma during pregnancy, labor, and delivery. J Clin Endocrinol Metab 1987; 64:224.
  64. Robinson BG, Emanuel RL, Frim DM, Majzoub JA. Glucocorticoid stimulates expression of corticotropin-releasing hormone gene in human placenta. Proc Natl Acad Sci U S A 1988; 85:5244.
  65. Potter E, Behan DP, Fischer WH, et al. Cloning and characterization of the cDNAs for human and rat corticotropin releasing factor-binding proteins. Nature 1991; 349:423.
  66. Petraglia F, Benedetto C, Florio P, et al. Effect of corticotropin-releasing factor-binding protein on prostaglandin release from cultured maternal decidua and on contractile activity of human myometrium in vitro. J Clin Endocrinol Metab 1995; 80:3073.
  67. McLean M, Bisits A, Davies J, et al. A placental clock controlling the length of human pregnancy. Nat Med 1995; 1:460.
  68. Challis JR, Matthews SG, Van Meir C, Ramirez MM. Current topic: the placental corticotrophin-releasing hormone-adrenocorticotrophin axis. Placenta 1995; 16:481.
  69. Clifton VL, Read MA, Leitch IM, et al. Corticotropin-releasing hormone-induced vasodilatation in the human fetal-placental circulation: involvement of the nitric oxide-cyclic guanosine 3',5'-monophosphate-mediated pathway. J Clin Endocrinol Metab 1995; 80:2888.
  70. Chakravorty A, Mesiano S, Jaffe RB. Corticotropin-releasing hormone stimulates P450 17alpha-hydroxylase/17,20-lyase in human fetal adrenal cells via protein kinase C. J Clin Endocrinol Metab 1999; 84:3732.
  71. Smith R, Mesiano S, Chan EC, et al. Corticotropin-releasing hormone directly and preferentially stimulates dehydroepiandrosterone sulfate secretion by human fetal adrenal cortical cells. J Clin Endocrinol Metab 1998; 83:2916.
  72. Aggelidou E, Hillhouse EW, Grammatopoulos DK. Up-regulation of nitric oxide synthase and modulation of the guanylate cyclase activity by corticotropin-releasing hormone but not urocortin II or urocortin III in cultured human pregnant myometrial cells. Proc Natl Acad Sci U S A 2002; 99:3300.
  73. Wadhwa PD, Garite TJ, Porto M, et al. Placental corticotropin-releasing hormone (CRH), spontaneous preterm birth, and fetal growth restriction: a prospective investigation. Am J Obstet Gynecol 2004; 191:1063.
  74. Potestio FA, Zakar T, Olson DM. Glucocorticoids stimulate prostaglandin synthesis in human amnion cells by a receptor-mediated mechanism. J Clin Endocrinol Metab 1988; 67:1205.
  75. Marinoni E, Korebrits C, Di Iorio R, et al. Effect of betamethasone in vivo on placental corticotropin-releasing hormone in human pregnancy. Am J Obstet Gynecol 1998; 178:770.
  76. Korebrits C, Yu DH, Ramirez MM, et al. Antenatal glucocorticoid administration increases corticotrophin-releasing hormone in maternal plasma. Br J Obstet Gynaecol 1998; 105:556.
  77. Wadhwa PD, Porto M, Garite TJ, et al. Maternal corticotropin-releasing hormone levels in the early third trimester predict length of gestation in human pregnancy. Am J Obstet Gynecol 1998; 179:1079.
  78. Pitera AE, Smith GC, Wentworth RA, Nathanielsz PW. Parathyroid hormone-related peptide (1 to 34) inhibits in vitro oxytocin-stimulated activity of pregnant baboon myometrium. Am J Obstet Gynecol 1998; 179:492.
  79. Ambrus G, Rao CV. Novel regulation of pregnant human myometrial smooth muscle cell gap junctions by human chorionic gonadotropin. Endocrinology 1994; 135:2772.
  80. MacLennan AH, Nicolson R, Green RC. Serum relaxin in pregnancy. Lancet 1986; 2:241.
  81. Bell RJ, Permezel M, MacLennan A, et al. A randomized, double-blind, placebo-controlled trial of the safety of vaginal recombinant human relaxin for cervical ripening. Obstet Gynecol 1993; 82:328.
  82. Romero R, Avila C, Brekus CA, Morotti R. The role of systemic and intrauterine infection in preterm parturition. Ann N Y Acad Sci 1991; 622:355.
  83. Osmers RG, Bläser J, Kuhn W, Tschesche H. Interleukin-8 synthesis and the onset of labor. Obstet Gynecol 1995; 86:223.
  84. Dudley DJ. Pre-term labor: an intra-uterine inflammatory response syndrome? J Reprod Immunol 1997; 36:93.
  85. Kelly RW. Inflammatory mediators and parturition. Rev Reprod 1996; 1:89.
  86. Norwitz ER, Bonney EA, Snegovskikh VV, et al. Molecular Regulation of Parturition: The Role of the "Decidual Clock". In: Molecular Approaches to Reproductive and Newborn Medicine, Bianchi DW, Norwitz ER. (Eds), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York 2015.
  87. Unal ER, Cierny JT, Roedner C, et al. Maternal inflammation in spontaneous term labor. Am J Obstet Gynecol 2011; 204:223.e1.
  88. Norwitz ER, López Bernal A, Starkey PM. Tumor necrosis factor-alpha selectively stimulates prostaglandin F2 alpha production by macrophages in human term decidua. Am J Obstet Gynecol 1992; 167:815.
  89. Mendelson CR. Minireview: fetal-maternal hormonal signaling in pregnancy and labor. Mol Endocrinol 2009; 23:947.
  90. Birkedal-Hansen H. Proteolytic remodeling of extracellular matrix. Curr Opin Cell Biol 1995; 7:728.
  91. Parry S, Strauss JF 3rd. Premature rupture of the fetal membranes. N Engl J Med 1998; 338:663.
  92. Vadillo-Ortega F, González-Avila G, Furth EE, et al. 92-kd type IV collagenase (matrix metalloproteinase-9) activity in human amniochorion increases with labor. Am J Pathol 1995; 146:148.
  93. Vadillo-Ortega F, Hernandez A, Gonzalez-Avila G, et al. Increased matrix metalloproteinase activity and reduced tissue inhibitor of metalloproteinases-1 levels in amniotic fluids from pregnancies complicated by premature rupture of membranes. Am J Obstet Gynecol 1996; 174:1371.
  94. Fortunato SJ, Menon R, Lombardi SJ. Presence of four tissue inhibitors of matrix metalloproteinases (TIMP-1, -2, -3 and -4) in human fetal membranes. Am J Reprod Immunol 1998; 40:395.
  95. Riley SC, Leask R, Denison FC, et al. Secretion of tissue inhibitors of matrix metalloproteinases by human fetal membranes, decidua and placenta at parturition. J Endocrinol 1999; 162:351.
  96. Maymon E, Romero R, Pacora P, et al. Human neutrophil collagenase (matrix metalloproteinase 8) in parturition, premature rupture of the membranes, and intrauterine infection. Am J Obstet Gynecol 2000; 183:94.
  97. Katsura M, Ito A, Hirakawa S, Mori Y. Human recombinant interleukin-1 alpha increases biosynthesis of collagenase and hyaluronic acid in cultured human chorionic cells. FEBS Lett 1989; 244:315.
  98. So T, Ito A, Sato T, et al. Tumor necrosis factor-alpha stimulates the biosynthesis of matrix metalloproteinases and plasminogen activator in cultured human chorionic cells. Biol Reprod 1992; 46:772.
  99. Simpson KL, Keelan JA, Mitchell MD. Labour-associated changes in the regulation of production of immunomodulators in human amnion by glucocorticoids, bacterial lipopolysaccharide and pro-inflammatory cytokines. J Reprod Fertil 1999; 116:321.
  100. Keelan JA, Sato TA, Gupta DK, et al. Prostanoid stimulation of cytokine production in an amnion-derived cell line: evidence of a feed-forward mechanism with implications for term and preterm labor. J Soc Gynecol Investig 2000; 7:37.
  101. Qin X, Chua PK, Ohira RH, Bryant-Greenwood GD. An autocrine/paracrine role of human decidual relaxin. II. Stromelysin-1 (MMP-3) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). Biol Reprod 1997; 56:812.
  102. Maradny EE, Kanayama N, Halim A, et al. Stretching of fetal membranes increases the concentration of interleukin-8 and collagenase activity. Am J Obstet Gynecol 1996; 174:843.
  103. Nemeth E, Tashima LS, Yu Z, Bryant-Greenwood GD. Fetal membrane distention: I. Differentially expressed genes regulated by acute distention in amniotic epithelial (WISH) cells. Am J Obstet Gynecol 2000; 182:50.
  104. Li W, Challis JR. Corticotropin-releasing hormone and urocortin induce secretion of matrix metalloproteinase-9 (MMP-9) without change in tissue inhibitors of MMP-1 by cultured cells from human placenta and fetal membranes. J Clin Endocrinol Metab 2005; 90:6569.