Skip to main content
SpringerLink
Log in

Neuropeptide Pathways Controlling the Timing of Birth

  • Chapter
  • First Online:
Neuroendocrine Regulation of Mammalian Pregnancy and Lactation

Part of the book series: Masterclass in Neuroendocrinology ((MANEURO,volume 15))

  • 68 Accesses

Abstract

The mechanisms regulating gestation length and birth differ markedly between species. In many mammals, corticotropin releasing hormone (CRH) plays a central role in the processes that trigger the progression from uterine quiescence to active labor. This results in processes being well coordinated with the maturation of the fetus and ensures sufficient maturation of fetal organ systems for successful extra-uterine life. In many mammalian species, CRH release and stimulation of the fetal hypothalamic-pituitary-adrenal (HPA) axis, with a consequent rise in cortisol levels, triggers the initiation of labor and birth. The onset of labor in women differs markedly, with initiation processes begun by rising levels of CRH produced by the syncytiotrophoblast of the placenta. This “placental clock” mechanism leads to increased production of estrogens toward term and a rise in the expression of contraction-associated proteins. A premature rise in CRH production leads to preterm labor in some instances; however, many cases of early preterm labor are started independently of these mechanisms and involve intra-uterine infection and inflammation. Oxytocin is a maternal signal triggering labor once the uterine tissues are adequately prepared, and has a role in setting the time of day that labor is initiated. Myometrial stimulation by oxytocin is also important in the final stages of birth for expulsion of the fetus, separation of the placenta, and for reducing postpartum bleeding. Synthetic oxytocin may be used to promote uterine contractions for the augmentation of labor. Recent observations therefore suggest that CRH and oxytocin have key roles in controlling the onset of labor in women, whereas early preterm birth is controlled differently, involving poorly understood inflammatory mechanisms.

https://www.newcastle.edu.au/profile/jon-hirst

https://www.newcastle.edu.au/profile/hannah-palliser

https://www.newcastle.edu.au/profile/julia-c-shaw

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ackerman WE, Zhang XL, Rovin BH, Kniss DA (2005) Modulation of cytokine-induced cyclooxygenase 2 expression by PPARG ligands through NFkappaB signal disruption in human WISH and amnion cells. Biol Reprod 73:527–535

    Article  CAS  PubMed  Google Scholar 

  • Adams Waldorf KM, Gravett MG, McAdams RM, Paolella LJ, Gough GM, Carl DJ, Bansal A, Liggitt HD, Kapur RP, Reitz FB, Rubens CE (2011) Choriodecidual group B streptococcal inoculation induces fetal lung injury without intra-amniotic infection and preterm labor in Macaca nemestrina. PLoS One 6:e28972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arthur P, Taggart MJ, Mitchell BF (2007) Oxytocin and parturition: a role for increased myometrial calcium and calcium sensitization? Front Biosci 12:619–633

    Article  CAS  PubMed  Google Scholar 

  • Ben-Ari Y, Khalilov I, Kahle KT, Cherubini E (2012) The GABA excitatory/inhibitory shift in brain maturation and neurological disorders. Neuroscientist 18:467–486

    Article  PubMed  Google Scholar 

  • Bertoni A, Schaller F, Tyzio R, Gaillard S, Santini F, Xolin M, Diabira D, Vaidyanathan R, Matarazzo V, Medina I, Hammock E, Zhang J, Chini B, Gaiarsa JL, Muscatelli F (2021) Oxytocin administration in neonates shapes hippocampal circuitry and restores social behavior in a mouse model of autism. Mol Psychiatry 26:7582–7595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bravo PW (1994) Reproductive endocrinology of llamas and alpacas. Vet Clin North Am Food Anim Pract 10:265–279

    Article  CAS  PubMed  Google Scholar 

  • Casey ML, MacDonald PC, Mitchell MD (1985) Despite a massive increase in cortisol secretion in women during parturition, there is an equally massive increase in prostaglandin synthesis. A paradox? J Clin Invest 75:1852–1857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Challis JR, Sloboda D, Matthews SG, Holloway A, Alfaidy N, Patel FA, Whittle W, Fraser M, Moss TJ, Newnham J (2001) The fetal placental hypothalamic-pituitary-adrenal (HPA) axis, parturition and post natal health. Mol Cell Endocrinol 185:135–144

    Article  CAS  PubMed  Google Scholar 

  • Challis JRG, Brooks AN (1989) Maturation and activation of hypothalamic-pituitary-adrenal function in fetal sheep. Endocr Rev 10:182–203

    Article  CAS  PubMed  Google Scholar 

  • Chan EC, Brinsmead MW, Chen SE, Nanra R, Simm B, McLean M, Smith R (1990) Urinary corticotropin-releasing hormone immunoreactivity is elevated during human pregnancy. Gynecol Endocrinol 4:233–244

    Article  CAS  PubMed  Google Scholar 

  • Coleman H, Hirst JJ, Parkington HC (2013) The GABAA excitation-to-inhibition switch in the hippocampus of the perinatal guinea pig. Fetal Neonatal Physiol Soc Proc 40

    Google Scholar 

  • Cook JL, Zaragoza DB, Sung DH, Olson DM (2000) Expression of myometrial activation and stimulation genes in a mouse model of preterm labor: myometrial activation, stimulation, and preterm labor. Endocrinology 141:1718–1728

    Article  CAS  PubMed  Google Scholar 

  • Erickson EN, Krol KM, Perkeybile AM, Connelly JJ, Myatt L (2022) Oxytocin receptor single nucleotide polymorphism predicts atony-related postpartum hemorrhage. BMC Pregnancy Childbirth 22:884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Erickson EN, Myatt L, Danoff JS, Krol KM, Connelly JJ (2023) Oxytocin receptor DNA methylation is associated with exogenous oxytocin needs during parturition and postpartum hemorrhage. Commun Med (Lond) 3:11

    Article  CAS  PubMed  Google Scholar 

  • Flenady V, Reinebrant HE, Liley HG, Tambimuttu EG, Papatsonis DN (2014) Oxytocin receptor antagonists for inhibiting preterm labour. Cochrane Database Syst Rev CD004452

    Google Scholar 

  • Flint AP, Forsling ML, Mitchell MD (1978) Blockade of the Ferguson reflex by lumbar epidural anaesthesia in the parturient sheep: effects on oxytocin secretion and uterine venous prostaglandin F levels. Horm Metab Res 10:545–547

    Article  CAS  PubMed  Google Scholar 

  • Goldsmith LT, Weiss G (2009) Relaxin in human pregnancy. Ann N Y Acad Sci 1160:130–135

    Article  CAS  PubMed  Google Scholar 

  • Gravett MG, Haluska GJ, Cook MJ, Novy MJ (1996) Fetal and maternal endocrine responses to experimental intrauterine infection in rhesus monkeys. Am J Obstet Gynecol 174:1725–1731; discussion 31-3

    Article  CAS  PubMed  Google Scholar 

  • Guo C, Wang W, Liu C, Myatt L, Sun K (2014) Induction of PGF2alpha synthesis by cortisol through GR dependent induction of CBR1 in human amnion fibroblasts. Endocrinology 155:3017–3024

    Article  PubMed  PubMed Central  Google Scholar 

  • Hassan HE, Othman AA, Eddington ND, Duffy L, Xiao L, Waites KB, Kaufman DA, Fairchild KD, Terrin ML, Viscardi RM (2011) Pharmacokinetics, safety, and biologic effects of azithromycin in extremely preterm infants at risk for ureaplasma colonization and bronchopulmonary dysplasia. J Clin Pharmacol 51:1264–1275

    Article  CAS  PubMed  Google Scholar 

  • Helmer H, Saleh L, Petricevic L, Knofler M, Reinheimer TM (2020) Barusiban, a selective oxytocin receptor antagonist: placental transfer in rabbit, monkey, and humandagger. Biol Reprod 103:135–143

    Article  PubMed  PubMed Central  Google Scholar 

  • Herrera CL, Bowman ME, McIntire DD, Nelson DB, Smith R (2021) Revisiting the placental clock: early corticotrophin-releasing hormone rise in recurrent preterm birth. PLoS One 16:e0257422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hertelendy F, Zakar T (2004) Prostaglandins and the myometrium and cervix. Prostaglandins Leukot Essent Fatty Acids 70:207–222

    Article  CAS  PubMed  Google Scholar 

  • Hirst JJ, Haluska GJ, Cook MJ, Novy MJ (1993) Plasma oxytocin and nocturnal uterine activity: maternal but not fetal concentrations increase progressively during late pregnancy and delivery in rhesus monkeys. Am J Obstet Gynecol 169:415–422

    Article  CAS  PubMed  Google Scholar 

  • Hirst JJ, Kelleher MA, Walker DW, Palliser HK (2014) Neuroactive steroids in pregnancy: key regulatory and protective roles in the foetal brain. J Steroid Biochem Mol Biol 139:144–153

    Article  CAS  PubMed  Google Scholar 

  • Hirst JJ, Palliser HK, Shaw JC, Crombie G, Walker DW, Zakar T (2018) Birth and neonatal transition in the guinea pig: experimental approaches to prevent preterm birth and protect the premature fetus. Front Physiol 9:1802

    Article  PubMed  PubMed Central  Google Scholar 

  • Hirst JJ, Teixeira FJ, Zakar T, Olson DM (1995) Prostaglandin H synthase-2 expression increases in human gestational tissues with spontaneous labour onset. Reprod Fertil Dev 7:633–637

    Article  CAS  PubMed  Google Scholar 

  • Hirst JJ, Walker DW, Yawno T, Palliser HK (2009) Stress in pregnancy: a role for neuroactive steroids in protecting the fetal and neonatal brain. Dev Neurosci 31:363–377

    Article  CAS  PubMed  Google Scholar 

  • Ishimoto H, Jaffe RB (2011) Development and function of the human fetal adrenal cortex: a key component in the feto-placental unit. Endocr Rev 32:317–355

    Article  CAS  PubMed  Google Scholar 

  • Ishimoto H, Minegishi K, Higuchi T, Furuya M, Asai S, Kim SH, Tanaka M, Yoshimura Y, Jaffe RB (2008) The periphery of the human fetal adrenal gland is a site of angiogenesis: zonal differential expression and regulation of angiogenic factors. J Clin Endocrinol Metab 93:2402–2408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ivell R, Kimura T, Muller D, Augustin K, Abend N, Bathgate R, Telgmann R, Balvers M, Tillmann G, Fuchs AR (2001) The structure and regulation of the oxytocin receptor. Exp Physiol 86:289–296

    Article  CAS  PubMed  Google Scholar 

  • Kaludjerovic J, Ward WE (2012) The interplay between estrogen and fetal adrenal cortex. J Nutr Metab 2012:837901

    Article  PubMed  PubMed Central  Google Scholar 

  • Karalis K, Muglia LJ, Bae D, Hilderbrand H, Majzoub JA (1997) CRH and the immune system. J Neuroimmunol 72:131–136

    Article  CAS  PubMed  Google Scholar 

  • Kelleher MA, Lee JY, Roberts VHJ, Novak CM, Baschat AA, Morgan TK, Novy MJ, Rasanen JP, Frias AE, Burd I (2020) Maternal azithromycin therapy for Ureaplasma parvum intraamniotic infection improves fetal hemodynamics in a nonhuman primate model. Am J Obstet Gynecol 223:578 e1–78 e11

    Article  PubMed  Google Scholar 

  • Khazipov R, Tyzio R, Ben-Ari Y (2008) Effects of oxytocin on GABA signalling in the foetal brain during delivery. Progress Brain Res 170:243–257

    Article  CAS  Google Scholar 

  • Komisaruk BR, Sansone G (2003) Neural pathways mediating vaginal function: the vagus nerves and spinal cord oxytocin. Scand J Psychol 44:241–250

    Article  PubMed  Google Scholar 

  • La Verde M, Riemma G, Torella M, Torre C, Cianci S, Conte A, Capristo C, Morlando M, Colacurci N, De Franciscis P (2022) Impact of Braxton-Hicks contractions on fetal wellbeing; a prospective analysis through computerised cardiotocography. J Obstet Gynaecol 42:569–573

    Article  PubMed  Google Scholar 

  • Leonzino M, Busnelli M, Antonucci F, Verderio C, Mazzanti M, Chini B (2016) The timing of the excitatory-to-inhibitory GABA switch is regulated by the oxytocin receptor via KCC2. Cell Rep 15:96–103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leung TN, Chung TK, Madsen G, McLean M, Chang AM, Smith R (1999) Elevated mid-trimester maternal corticotrophin-releasing hormone levels in pregnancies that delivered before 34 weeks. Br J Obstet Gynaecol 106:1041–1046

    Article  CAS  PubMed  Google Scholar 

  • Liggins GC (1969) Premature delivery of foetal lambs infused with glucocorticoids. J Endocrinol 45:515–523

    Article  CAS  PubMed  Google Scholar 

  • Lu Y, Zhou Q, Lu JW, Wang WS, Sun K (2019) Involvement of STAT3 in the synergistic induction of 11beta-HSD1 by SAA1 and cortisol in human amnion fibroblasts. Am J Reprod Immunol 82:e13150

    Article  PubMed  Google Scholar 

  • Mark PJ, Smith JT, Waddell BJ (2006) Placental and fetal growth retardation following partial progesterone withdrawal in rat pregnancy. Placenta 27:208–214

    Article  CAS  PubMed  Google Scholar 

  • McGrath S, McLean M, Smith D, Bisits A, Giles W, Smith R (2002) Maternal plasma corticotropin-releasing hormone trajectories vary depending on the cause of preterm delivery. Am J Obstet Gynecol 186:257–260

    Article  CAS  PubMed  Google Scholar 

  • McLean M, Bisits A, Davies J, Woods R, Lowry P, Smith R (1995) A placental clock controlling the length of human pregnancy. Nat Med 1:460–463

    Article  CAS  PubMed  Google Scholar 

  • McLean M, Smith R (2001) Corticotrophin-releasing hormone and human parturition. Reproduction 121:493–501

    Article  CAS  PubMed  Google Scholar 

  • Menon R, Lappas M, Zakar T (2021) Editorial: The role of the fetal membranes in pregnancy and birth. Front Physiol 12:653084

    Article  PubMed  PubMed Central  Google Scholar 

  • Migale R, MacIntyre DA, Cacciatore S, Lee YS, Hagberg H, Herbert BR, Johnson MR, Peebles D, Waddington SN, Bennett PR (2016) Modeling hormonal and inflammatory contributions to preterm and term labor using uterine temporal transcriptomics. BMC Med 14:86

    Article  PubMed  PubMed Central  Google Scholar 

  • Mitchell BF, Taggart MJ (2009) Are animal models relevant to key aspects of human parturition? Am J Physiol Regul Integr Comp Physiol 297:R525–R545

    Article  CAS  PubMed  Google Scholar 

  • Mitchell C, Johnson R, Bisits A, Hirst J, Zakar T (2011) PTGS2 (prostaglandin endoperoxide synthase-2) expression in term human amnion in vivo involves rapid mRNA turnover, polymerase-II 5'-pausing, and glucocorticoid transrepression. Endocrinology 152:2113–2122

    Article  CAS  PubMed  Google Scholar 

  • Mitchell CM, Johnson RF, Giles WB, Zakar T (2008) Prostaglandin H synthase-2 gene regulation in the amnion at labour: histone acetylation and nuclear factor kappa B binding to the promoter in vivo. Mol Hum Reprod 14:53–59

    Article  CAS  PubMed  Google Scholar 

  • Mitchell CM, Sykes SD, Pan X, Pringle KG, Lumbers ER, Hirst JJ, Zakar T (2013) Inflammatory and steroid receptor gene methylation in the human amnion and decidua. J Mol Endocrinol 50:267–277

    Article  CAS  PubMed  Google Scholar 

  • Olson DM, Mijovic JE, Zaragoza DB, Cook JL (2001) Prostaglandin endoperoxide H synthase type 1 and type 2 messenger ribonucleic acid in human fetal tissues throughout gestation and in the newborn infant. Am J Obstet Gynecol 184:169–174

    Article  CAS  PubMed  Google Scholar 

  • Olson DM, Skinner K, Challis JR (1983) Estradiol-17 beta and 2-hydroxyestradiol-17 beta-induced differential production of prostaglandins by cells dispersed from human intrauterine tissues at parturition. Prostaglandins 25:639–651

    Article  CAS  PubMed  Google Scholar 

  • Olson DM, Zakar T, Teixeira FJ, Hirst JJ, Guo F, Pankovich J (1993) Prostaglandins and parturition. In Morniex et al (ed) Progress in endocrinology 7:644–648

    Google Scholar 

  • Pan X, Bowman M, Scott RJ, Fitter J, Nicholson RC, Smith R, Zakar T (2015) Methylation of the corticotropin releasing hormone gene promoter in BeWo cells: relationship to gene activity. Int J Endocrinol 2015:861302

    Article  PubMed  PubMed Central  Google Scholar 

  • Phung J, Wang C, Reeders J, Zakar T, Paul JW, Tyagi S, Pennell CE, Smith R (2022) Preterm labor with and without chorioamnionitis is associated with activation of myometrial inflammatory networks: a comprehensive transcriptomic analysis. Am J Obstet Gynecol

    Google Scholar 

  • Quinn TA, Ratnayake U, Dickinson H, Castillo-Melendez M, Walker DW (2016) The feto-placental unit, and potential roles of dehydroepiandrosterone (DHEA) in prenatal and postnatal brain development: a re-examination using the spiny mouse. J Steroid Biochem Mol Biol 160:204–213

    Article  CAS  PubMed  Google Scholar 

  • Schwartz J, McMillen IC (2001) Fetal hypothalamus-pituitary-adrenal axis on the road to parturition. Clin Exp Pharmacol Physiol 28:108–112

    Article  CAS  PubMed  Google Scholar 

  • Smith R, Paul J, Maiti K, Tolosa J, Madsen G (2012) Recent advances in understanding the endocrinology of human birth. Trends Endocrinol Metab 23:516–523

    Article  CAS  PubMed  Google Scholar 

  • Smith R, Zakar T, Madsen G (2013) Mammalian labor: variations on a theme by amniota. Endocrinology 154:584–588

    Article  CAS  PubMed  Google Scholar 

  • Smith R, Van Helden D, Hirst J, Zakar T, Read M, Chan E-C, Palliser H, Grammatopoulos D, Nicholson R, Parkington HC (2007) Pathological interactions with the timing of birth and uterine activation. Austral New Zeal J Obstet Gynaecol 47:430–437

    Article  Google Scholar 

  • Son M, Roy A, Grobman WA, Miller ES, Dude A, Peaceman AM, Stetson B (2023) Maximum dose rate of intrapartum oxytocin infusion and associated obstetric and perinatal outcomes. Obstet Gynecol 141:379–386

    Article  CAS  PubMed  Google Scholar 

  • Sun K, Ma R, Cui X, Campos B, Webster R, Brockman D, Myatt L (2003) Glucocorticoids induce cytosolic phospholipase A2 and prostaglandin H synthase type 2 but not microsomal prostaglandin E synthase (PGES) and cytosolic PGES expression in cultured primary human amnion cells. J Clin Endocrinol Metab 88:5564–5571

    Article  CAS  PubMed  Google Scholar 

  • Terzidou V, Blanks AM, Kim SH, Thornton S, Bennett PR (2011) Labor and inflammation increase the expression of oxytocin receptor in human amnion. Biol Reprod 84:546–552

    Article  CAS  PubMed  Google Scholar 

  • Thorburn GD, Challis JR (1979) Endocrine control of parturition. Physiol Rev 59:863–918

    Article  CAS  PubMed  Google Scholar 

  • Tyzio R, Holmes GL, Ben-Ari Y, Khazipov R (2007) Timing of the developmental switch in GABA(A) mediated signaling from excitation to inhibition in CA3 rat hippocampus using gramicidin perforated patch and extracellular recordings. [Erratum appears in Epilepsia. 2007 Dec;48(12):2380]. Epilepsia 48(Suppl 5):96–105

    Article  CAS  PubMed  Google Scholar 

  • Tyzio R, Minlebaev M, Rheims S, Ivanov A, Jorquera I, Holmes GL, Zilberter Y, Ben-Ari Y, Khazipov R (2008) Postnatal changes in somatic gamma-aminobutyric acid signalling in the rat hippocampus. Eur J Neurosci 27:2515–2528

    Article  PubMed  Google Scholar 

  • Vannuccini S, Bocchi C, Severi FM, Challis JR, Petraglia F (2016) Endocrinology of human parturition. Annales d Endocrinologie 77:105–113

    Article  PubMed  Google Scholar 

  • Viscardi RM (2010) Ureaplasma species: role in diseases of prematurity. Clin Perinatol 37:393–409

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang A, Nie W, Li H, Hou Y, Yu Z, Fan Q, Sun R (2014) Epigenetic upregulation of corticotrophin-releasing hormone mediates postnatal maternal separation-induced memory deficiency. PLoS One 9:e94394

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang LY, Wang WS, Wang YW, Lu JW, Lu Y, Zhang CY, Li WJ, Sun K, Ying H (2019) Drastic induction of MMP-7 by cortisol in the human amnion: implications for membrane rupture at parturition. Faseb J 33:2770–2781

    Article  CAS  PubMed  Google Scholar 

  • Wang WS, Guo CM, Sun K (2020) Cortisol regeneration in the fetal membranes, a coincidental or requisite event in human parturition? Front Physiol 11:462

    Article  PubMed  PubMed Central  Google Scholar 

  • Weiss G (2013) Relaxin and the control of primate parturition. Ital J Anatomy Embryol 118:17–18

    Google Scholar 

  • Welsh TN, Hirst JJ, Palliser H, Zakar T (2014) Progesterone receptor expression declines in the guinea pig uterus during functional progesterone withdrawal and in response to prostaglandins. PLoS One 9:e105253

    Article  PubMed  PubMed Central  Google Scholar 

  • Whittle WL, Patel FA, Alfaidy N, Holloway AC, Fraser M, Gyomorey S, Lye SJ, Gibb W, Challis JR (2001) Glucocorticoid regulation of human and ovine parturition: the relationship between fetal hypothalamic-pituitary-adrenal axis activation and intrauterine prostaglandin production. Biol Reprod 64:1019–1032

    Article  CAS  PubMed  Google Scholar 

  • You X, Liu J, Xu C, Liu W, Zhu X, Li Y, Sun Q, Gu H, Ni X (2014) Corticotropin-releasing hormone (CRH) promotes inflammation in human pregnant myometrium: the evidence of CRH initiating parturition? J Clin Endocrinol Metab 99:E199–E208

    Article  CAS  PubMed  Google Scholar 

  • Young IR, Deayton JM, Hollingworth SA, Thorburn GD (1996) Continuous intrafetal infusion of prostaglandin E2 prematurely activates the hypothalamo-pituitary-adrenal axis and induces parturition in sheep. Endocrinology 137:2424–2431

    Article  CAS  PubMed  Google Scholar 

  • Zakar T, Mitchell BF (1996) The endocrinology of late pregnancy and parturition. In: Advances in organ biology. JAI Press

    Google Scholar 

  • Zakar T, Hertelendy F (2007) Progesterone withdrawal: key to parturition. Am J Obstet Gynecol 196:289–296

    Article  CAS  PubMed  Google Scholar 

  • Zakar T, Teixeira FJ, Hirst JJ, Guo F, MacLeod EA, Olson DM (1994) Regulation of prostaglandin endoperoxide H synthase by glucocorticoids and activators of protein kinase C in the human amnion. J Reprod Fertil 100:43–50

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

JJH, HKP, and JCS are supported by the National Health and Medical Research Council of Australia and receive additional support from the Hunter Medical Research Institute (HMRI).

Key References (see main list for reference details)

  • Herrera, C.L., et al., (2021). This paper describes the most recent information on the role of rising CRH in the initiation of term birth and the “placental clock.” The studies outline some of the problems with CRH measurement and give validated values for CRH changes during pregnancy and at term.

  • Mitchell, B.F., et al., (2013). The paper describes work outlining the key similarities and differences between animal models of term and preterm labor and the control of labor onset in women.

  • Mitchell, C.M., (2014). This study demonstrates the key role of DNA methylation in the expression of key genes involved in the shifting of uterine quiescence to an activated state. The work shows that differences in methylation may control the sensitivity of these genes to labor-triggering stimulation.

  • Vannuccini, S., et al., (2016). This paper provides a very good review of the pathways that lead to the onset of human labor, including the role of contraction-associated proteins and prostaglandins in the regulation of myometrial activity and in the breakdown of cervical connective tissue and cervical dilation.

  • Viscardi, R. M., et al., (2010). This study examined the role of intrauterine infection in preterm labor. The work particularly demonstrated the role of the relatively difficult to detect ureaplasma species in early preterm birth.

Author information

Authors and Affiliations

  1. School of Biomedical Sciences and Pharmacy, University of Newcastle & Mothers and Babies Research Program, Hunter Medical Research Institute, Newcastle, Australia

    Jonathan J. Hirst, Hannah K. Palliser & Julia C. Shaw

  2. School of Medicine and Public Health, University of Newcastle & Mothers and Babies Research Program, Hunter Medical Research Institute, Newcastle, Australia

    Tamas Zakar

Authors
  1. Jonathan J. Hirst
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hannah K. Palliser
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Julia C. Shaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tamas Zakar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonathan J. Hirst .

Editor information

Editors and Affiliations

  1. Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK

    Paula J. Brunton

  2. Centre for Neuroendocrinology, Department of Anatomy, University of Otago, Dunedin, New Zealand

    David R. Grattan

Rights and permissions

Reprints and permissions

Copyright information

© 2024 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Hirst, J.J., Palliser, H.K., Shaw, J.C., Zakar, T. (2024). Neuropeptide Pathways Controlling the Timing of Birth. In: Brunton, P.J., Grattan, D.R. (eds) Neuroendocrine Regulation of Mammalian Pregnancy and Lactation. Masterclass in Neuroendocrinology, vol 15. Springer, Cham. https://doi.org/10.1007/978-3-031-51138-7_5

Download citation

Publish with us

Policies and ethics

Search

Navigation