Abstract
Background
Despite impressive progress in the science and technology of reproduction, the mechanism by which labour is initiated in humans remains obscure.
Objectives
As the labour in humans is a distinct event differs from what happens in animals, this study aims to gather the current theories that could explain when and why the onset of human parturition occurs.
Methods
In a comprehensive review study done at the School of Medicine and Dentistry, University of Bristol, United Kingdom, MetaLib, the university web-based electronic library, was cross-searched for the factors behind the onset of labour in humans through different medical databases such as; Allied and Complementary Medicine Database (AMED), BIOSIS Previews on Web of Knowledge, PubMed, Cochrane Library, Medline and Web of Science, in-addition to the relevant printed medical journals and periodicals.
Results
The study revealed that among the potential factors involved in the process of human parturition are the changes in hormonal levels of estrogen and progesterone, increased production of prostaglandins and oxytocin, and the high levels of corticotrophin releasing hormone and cortisol are some among the potential factors involved in the process of human parturition. Inflammatory reactions with the release of cytokines are among the most accepted theories for term and preterm labours. It is most likely that the interaction between all these factors and others, yet to be discovered, play in harmony to initiate the process of labour in women.
Conclusion
The result show that birth is a result of complex, partially defined, events that are tightly regulated by a variety of mechanisms and mediators of endocrine, nervous and immune systems. Unfortunately, none of them is completely elucidated.
Similar content being viewed by others
References
Nathanielsz P (1996) The timing of birth. Am Sci 84:562–569
Bernal AL (2004) Overview of current research in parturition. Uterine contractility symposium. Exp Physiol J 86(2):213–222
Navitsky J, Greene JF, Curry SL (2000) The onset of human labour: current theories. Prim Care Update Ob Gyns 7(5):197–199
Vidaeff AC, Ramin SM (2008) Potential biochemical events associated with initiation of labour. Curr Med Chem 15(6):614–619
Pieber D, Allport VC, Hills F, Johnson M, Bennett PR (2001) Interactions between progesterone receptor isoforms in myometrial cells in human labour. Mol Hum Reprod 7(9):875–879
Mesiano S, Chan E-C, Fitter JT, Kwek K, Yeo G, Smith R (2002) Progesterone withdrawal and estrogen activation in human parturition are coordinated by progesterone receptor A expression in the myometrium. J Clin Endocrinol Metab 87(6):2924–2930
Speroff L, Fritz MA (2005) The endocrinology of parturition. In: Clinical gynecologic endocrinology and infertility, 7th edn. Lippincott Williams and Wilkins Co. Chapter 8:295–315
Astle S, Slater DM, Thornton S (2003) The involvement of progesterone in the onset of human labour. Euro J Obstet Gynecol Reprod Biol 108(2):177–181
Zakar T, Hertelendy F (2007) Progesterone withdrawal: key to parturition. Am J Obstet Gynecol 196(4):289–296
Brown AG, Leite RS, Strauss JF 3rd (2004) Mechanisms underlying functional progesterone withdrawal at parturition. Ann N Y Acad Sci 1034:36–49
Mesiano S (2004) Myometrial progesterone responsiveness and the control of human parturition. J Soc Gynecol Investig 11(4):193–202
Sheehanl PM, Rice GE, Moses EK, Brennecke SP (2005) 5β-Dihydroprogesterone and steroid 5β-reductase decrease in association with human parturition at term. Mol Hum Reprod 11(7–8):495–501
Andersson S, Minjarez D, Yost NP, Word RA (2008) Estrogen and progesterone metabolism in the cervix during pregnancy and parturition. J Clin End Metab 93(6):2366–2374
Romero R, Munoz H, Gomez R, Parra M, Polanco M et al (1996) Increase in prostaglandin bioavailability precedes the onset of human parturition. Prostaglandins Leukot Essent Fatty Acids 54(3):187–191
Allport VC, Pieber D, Slater DM, Newton R, White JO, Bennett PR (2001) Human labour is associated with nuclear factor-кB activity which mediates cyclo-oxygenase-2 expression and is involved with the functional progesterone withdrawal. Mol Hum Reprod 7(6):581–586
Fischer DP, Hutchinson JA, Farrar D, O’Donovan PJ, Woodward DF, Marshall KM (2008) Loss of prostaglandin F2 alpha, but not thromboxane, responsiveness in pregnant human myometrium during labour. J Endocrinol 197(1):171–179
Romero R, Baumann P, Gonzalez R, Gomez R, Rittenhouse L, Behnke E, Mitchell MD (1994) Amniotic fluid prostanoid concentrations increase early during the course of spontaneous labor at term. Am J Obstet Gynecol 171(6):1613–1620
Bernal AL, Bryant-Greenwood GD, Hansell DJ, Hicks BR, Greenwood FC, Tumbull AC (1987) Effect of relaxin on prostaglandin E production by human amnion: changes in relation to the onset of labour. BJOG 94(11):1045–1051
Wathes DC, Borwick SC, Timmons PM, Leung ST, Thornton S (1999) Oxytocin receptor expression in human term and preterm gestational tissues prior to and following the onset of labour. J Endocrinol 161(1):143–151
Blanks AM, Thornton S (2003) The role of oxytocin in parturition. BJOG 110(4):46–51
Akerlund M (2004) Vasopressin and oxytocin in normal reproduction and in the pathophysiology of preterm labour and primary dysmenorrhea. Development of receptor antagonists for therapeutic use in these conditions. Rocz Akad Med Bialymst 49:18–21 (Source: Pub-Medline search)
Fuchs AR, Fuchs F, Husslein P, Soloff MS, Fernstrom MJ (1982) Oxytocin receptors and human parturition: a dual role for oxytocin in the initiation of labour. Science 215(4538):1396–1398
Johnson MH (2007) Parturition. In: Johnson MH (ed) Johnson and Everitt’s essential reproduction. Blackwell Publishing Co., 6th edn. Chapter 13:245–54
Rehman KS, Sirianni R, Parker R, Rainey WE, Carr BR (2007) The regulation of adrenocorticotrophic hormone receptor by corticotropin-releasing hormone in human fetal adrenal definitive/transitional zone cells. J Reprod Sci 14(6):578–587
McLean M, Smith R (2001) Corticotrophin-releasing hormone and human parturition. J Reprod 121:493–501
Izzo A, Rotondi M, Perone C, Lauro C, Manzo E, Casilli B, Rasile M, Amato G (1999) Inhibitory effect of exogenous oxytocin on ACTH and cortisol secretion during labour. Clin Exp Obstet Gynecol 26(3–4):221–224
Markovic D, Vatish M, Gu M, Slater D, Newton R, Lehnert H, Grammatopoulos DK (2007) The onset of labor alters corticotropin-releasing hormone type 1 receptor variant expression in human myometrium: putative role of interleukin-1 beta. Endocrinology 148(7):3205–3213
Marton IS (1988) Fetal adrenal steroid: initiation of human parturition. Acta Physiol Hung 71(4):557–559
Keelan JA, Marvin KW, Sato TA, McCowan LM, Coleman M et al (1999) Concentrations of activin-A, inhibin-A, and follistatin in human amnion, choriodecidual and placental tissues at term and preterm. J Endocrinol 163:99–106
Rae K, Hollebone K, Chetty V, Clausen D, McFarlane J (2007) Follistatin serum concentrations during full-term labour in women: significant differences between spontaneous and induced labour. J Reprod 134(5):705–711
Wang EY, Woodruff TK, Moawad A, National Institute of Child Health and Human Development, Maternal-Fetal Medicine Units Network (2002) Follistatin-free activin A is not associated with preterm birth. Am J Obstet Gynecol 186(3):464–469
Gustafsson C, Hummerdal P, Matthiesen L, Berg G, Ekerfelt C, Ernerudh J (2006) Cytokines secretion in decidual mononuclear cells from term human pregnancy with or without labour: ELISPOT detection of IFN-gamma, IL-4, IL-10, TGF-beta and TNF-alpha. J Reprod Immunol 71(1):41–56
Tattersall M, Engineer N, Khanjani S, Sooranna SR, Roberts VH et al (2008) Pro-labour myometrial gene expression: are preterm labour and term labour the same? J Reprod 135(4):569–579
Keelan JA, Blumenstein M, Helliwell RJ, Sato TA, Marvin KW, Mitchell MD (2003) Cytokines, prostaglandins and parturition: a review. J Placenta 24(S1):33–46
Lee Y, Allport V, Sykes A, Lindstrom T, Slater D, Bennett D (2003) The effects of labour and of interleukin 1 beta upon the expression of nuclear factor kappa B related proteins in human amnion. Mole Hum Reprod 9(4):213–218
Lindström TM, Bennett PR (2005) The role of nuclear factor kappa B in human labour. J Reprod 130:569–581
Lappas M, Rice GE (2008) Transcriptional regulation of the processes of human labour and delivery. J Placenta 30(Suppl):90–95
Zicari A, Ticconi C, Realacci M, Cela O, Santangelo C, Pietropolli A, Russo MA, Piccione E (2002) Hormonal regulation of cytokine release by human fetal membranes at term gestation: effects of oxytocin, hydrocortisone and progesterone on tumour necrosis factor alpha and transforming growth factor beta 1 output. J Reprod Immunol 56(1–2):123–136
Hayashi M, Zhu K, Sagesaka T, Fukasawa I, Inaba N (2008) Amniotic fluid levels of tumour necrosis factor-alpha and soluble tumour necrosis factor receptor 1 before and after the onset of labour in normal pregnancies. Horm Metab Res 40(4):251–256
Steinborn A, Sohn C, Hegar S, Niederhut A, Hildenbrand R, Kaufmann M (1999) Labour-associated expression of intracellular adhesion molecule-1 (ICAM-1) in placental endothelial cells indicates participation of immunological processes in parturition. J Placenta 20(7):567–573
Tsatas D, Baker MS, Rice GE (1999) Differential expression of proteases in human gestational tissue before, during and after spontaneous onset labour at term. J Reprod Fertil 116(1):43–49
Winkler M, Fischer DC, Ruck P, Marx T, Kaiserling E et al (1999) Parturition at term: parallel increases in interleukin-8 and proteinase concentrations and neutrophil count in the lower uterine segment. Hum Reprod 14(4):1096–1100
Di Quinzio MK, Georgious HM, Holdsworth-Carson SJ, Ayhan M, Heng YJ et al (2008) Proteomic analysis of human cervico-vaginal fluid displays differential protein expression in association with labour onset at term. J Proteome Res 7(5):1916–1921
Paine MA, Scioscia M, Gumaa KA, Rodeck CH, Rademacher TW (2006) P-type inosito phosphoglycans in serum and amniotic fluid in active pre-eclampsia. J Reprod Immunol 69(2):165–179
Scioscia M, Paine MA, Gumaa KA, Rodeck CH, Rademacher TW (2008) Release of inositol phosphoglycan P-type by the human placenta following insulin stimulus: a multiple comparison between pre-eclampsia, intrauterine growth restriction and gestational hypertension. J Maternal-Fetal Neonatal Med 21(8):581–585
Paine MA, Rodeck CH, Williams PJ, Rademacher TW (2003) Possible involvement of inositol phosphoglycan-P in human parturition. J Reprod Immunol 59(2):267–275
Kumar D, Fung W, Moore R, Pandey V, Fox J et al (2006) Proinflammatory cytokines found in amniotic fluid induce collagen remodeling, apoptosis, and biophysical weakening of cultured human fetal membranes. Biol Reprod 74(1):29–34
Hsu C-D, Meaddough E, Basherra H, Harirah H, Lu L-C (2000) Increased apoptosis in human amnion is associated with labour at term. Am J Reprod Immunol 43(5):255–258
Kumagai K, Otsuki Y, Ito Y, Shibata MA, Abe H, Ueki M (2001) Apoptosis in the normal human amnion at term, independent of Bcl-2 regulation and onset of labour. Mol Hum Reprod 7(7):681–689
Moore F, Bernal AL (2001) Myosin light chain kinase and the onset of labour in humans. Exp Physiol 86(2):313–318
Calder AA (2007) Normal labour. In: Edmonds DK (ed) Dewhurst’s textbook of obstetrics and gynaecology. Blackwell Publishing Co., 7th edn. Chapter 6:46–49
Suzuki H, Morishita S (1999) The relationship between the onset of labour mechanisms and the hemostatic system. Immunopharmacology 43(2–3):133–140
Patel RR, Steer P, Doyle P, Little MP, Elliott P (2004) Does gestation vary by ethnic group? A London-based study of over 122000 pregnancies with spontaneous onset of labour. Intern J Epidemiol 33(1):107–113
Ali KZ, Ali ME, Khalid ME (1996) High altitude and spontaneous preterm birth. Intern J Gynaecol Obstet 54(1):11–15
Ali KZ, Ali ME, Khalid ME (1997) Full-term birth weight and placental morphology at high and low altitude. Intern J Gynaecol Obstet 57(3):259–265
Chaudhari BP, Plunkett J, Ratajczak CK, Shen TT, DeFranco EA, Muglia LJ (2008) The genetics of birth timing: insights into a fundamental component of human development. Clin Genet 74(6):493–501
Chaiworapongsa T, Hong JS, Hull WM, Kim CJ, Gomez R et al (2008) The concentration of surfactant protein A in amniotic fluid decreases in spontaneous human parturition at term. J Maternal-Fetal Neon Med 21(9):652–659
Bernal AL, Phizackerley PJ (2000) Fetal surfactant as a source of arachidonate in human amniotic fluid. Prostaglandins Other Lipid Mediat 60(1–3):59–70
Driscoll DM, Merker DG (1984) A search for associations between weather and the onset of human parturition. Intern J Biomet 28(3):211–224
King EA, Fleschler RG, Cohen SM (1997) Association between significant decrease in barometric pressure and onset of labor. J Nurse-Midwifery 42(1):32–34
Stern EW, Glazer GL, Sanduleak N (1988) Influence of the full and new moon on onset of labour and spontaneous rupture of membranes. J Nurse-Midwifery 33(2):57–61
Zeitlin J, Saurel-Cubizolles M-J, de Mouzon J, Rivera L, Ancel P-Y et al (2002) Fetal sex and preterm birth: are males at greater risk? Hum Reprod 17(10):2762–2768
Zeitlin J, Ancel P-Y, Larroque B, Kaminski M, EPIPAGE Group (2004) Fetal sex and indicated very preterm birth: results of the EPIPAGE study. Am J Obstet Gynecol 190(5):1322–1325
Conflict of interest
I have no competing interests.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kamel, R.M. The onset of human parturition. Arch Gynecol Obstet 281, 975–982 (2010). https://doi.org/10.1007/s00404-010-1365-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00404-010-1365-9