Objective Over half of twin pregnancies in US and UK deliver prematurely but the reasons for this are unclear. The contractility of myometrium from twin pregnancies has not been directly investigated. The objective of this research was to determine if there are differences in the contractile activity and response to oxytocin, between myometrium from singleton and twin pregnancies, across a range of gestational ages. Furthermore, we wished to determine if contractile activity correlates with increasing level of stretch, using neonatal birth weights as a marker of uterine stretch. Methods This was an in vitro, laboratory based study of myometrial contractility in women pregnant with one or two babies, using biopsies obtained from non-labouring women undergoing Caesarean section. Spontaneous, oxytocin-stimulated and depolarization induced contractile activity was compared. Results Direct measurements of myometrial contractility under controlled conditions show that the frequency of contractions and responses to oxytocin are significantly increased in twins compared to singletons. The duration of contraction however was significantly reduced. We find that contractile activity correlates with increasing levels of stretch, using neonatal birth weights as a surrogate for uterine stretch, with response to oxytocin being significantly positively correlated with birth weight. Conclusions We have found significant differences in contractile properties between myometrium from singleton and twin pregnancies and that increasing uterine stretch can alter the contractile properties of myometrium. We discuss the implication of these findings to preterm delivery and future studies.
References
[1]
Blanks AM, Shmygol A, Thornton S (2007) Preterm labour. Myometrial function in prematurity. Best practice & research Clinical obstetrics & gynaecology 21: 807–819.
[2]
Turton P, Neilson JP, Quenby S, Burdyga T, Wray S (2009) A short review of twin pregnancy and how oxytocin receptor expression may differ in multiple pregnancy. European journal of obstetrics, gynecology, and reproductive biology 144 Suppl 1S40–44.
[3]
Newman RB, Ellings JM, O'Reilly MM, Brost BC, Miller MC 3rd, et al (1997) Correlation of antepartum uterine activity and cervical change in twin gestation. Acta geneticae medicae et gemellologiae 46: 1–7.
[4]
Newman RB, Gill PJ, Campion S, Katz M (1989) The influence of fetal number on antepartum uterine activity. Obstetrics and gynecology 73: 695–699.
[5]
Morrison JC, Chauhan SP, Magann EF, Istwan NB, Rhea D, et al. (2005) Excessive uterine contractions: effect on the incidence of preterm delivery in twin gestation. The Journal of reproductive medicine 50: 923–927.
[6]
Hernandez AR, Gonzalez-Quintero VH, Istwan N, Rhea D, Vazquez-Vera E, et al. (2008) Antepartum uterine contraction patterns in twin pregnancies with and without preterm labor and delivering before or after 36 weeks. American journal of obstetrics and gynecology 198: e28–29.
[7]
Reichmann JP (2009) Home uterine activity monitoring: an evidence review of its utility in multiple gestations. The Journal of reproductive medicine 54: 559–562.
[8]
Sfakianaki AK, Buhimschi IA, Pettker CM, Magloire LK, Turan OM, et al.. (2008) Ultrasonographic evaluation of myometrial thickness in twin pregnancies. American journal of obstetrics and gynecology 198: 530 e531–510.
[9]
Lyall F, Lye S, Teoh T, Cousins F, Milligan G, et al. (2002) Expression of Gsalpha, connexin-43, connexin-26, and EP1, 3, and 4 receptors in myometrium of prelabor singleton versus multiple gestations and the effects of mechanical stretch and steroids on Gsalpha. Journal of the Society for Gynecologic Investigation 9: 299–307.
[10]
Al-Qahtani S, Heath A, Quenby S, Dawood F, Floyd R, et al. (2012) Diabetes is associated with impairment of uterine contractility and high Caesarean section rate. Diabetologia 55: 489–498.
[11]
Quenby S, Matthew A, Zhang J, Dawood F, Wray S (2011) In vitro myometrial contractility reflects indication for caesarean section. BJOG: an international journal of obstetrics and gynaecology 118: 1499–1506.
[12]
Luckas MJ, Wray S (2000) A comparison of the contractile properties of human myometrium obtained from the upper and lower uterine segments. BJOG: an international journal of obstetrics and gynaecology 107: 1309–1311.
[13]
Kupittayanant S, Luckas MJ, Wray S (2002) Effect of inhibiting the sarcoplasmic reticulum on spontaneous and oxytocin-induced contractions of human myometrium. BJOG: an international journal of obstetrics and gynaecology 109: 289–296.
[14]
Taggart MJ, Menice CB, Morgan KG, Wray S (1997) Effect of metabolic inhibition on intracellular Ca2+, phosphorylation of myosin regulatory light chain and force in rat smooth muscle. The Journal of physiology 499 (Pt 2): 485–496.
[15]
Crichton CA, Taggart MJ, Wray S, Smith GL (1993) Effects of pH and inorganic phosphate on force production in alpha-toxin-permeabilized isolated rat uterine smooth muscle. The Journal of physiology 465: 629–645.
[16]
Shmygol A, Noble K, Wray S (2007) Depletion of membrane cholesterol eliminates the Ca2+-activated component of outward potassium current and decreases membrane capacitance in rat uterine myocytes. The Journal of physiology 581: 445–456.
[17]
Heaton RC, Wray S, Eisner DA (1993) Effects of metabolic inhibition and changes of intracellular pH on potassium permeability and contraction of rat uterus. The Journal of physiology 465: 43–56.
[18]
Shmigol AV, Eisner DA, Wray S (1999) The role of the sarcoplasmic reticulum as a Ca2+ sink in rat uterine smooth muscle cells. The Journal of physiology 520 Pt 1: 153–163.
[19]
Floyd R, Wray S (2007) Calcium transporters and signalling in smooth muscles. Cell calcium 42: 467–476.
[20]
Ou CW, Chen ZQ, Qi S, Lye SJ (1998) Increased expression of the rat myometrial oxytocin receptor messenger ribonucleic acid during labor requires both mechanical and hormonal signals. Biology of reproduction 59: 1055–1061.
[21]
Parry LJ, Bathgate RA, Shaw G, Renfree MB, Ivell R (1997) Evidence for a local fetal influence on myometrial oxytocin receptors during pregnancy in the tammar wallaby (Macropus eugenii). Biology of reproduction 56: 200–207.
[22]
Terzidou V, Sooranna SR, Kim LU, Thornton S, Bennett PR, et al. (2005) Mechanical stretch up-regulates the human oxytocin receptor in primary human uterine myocytes. The Journal of clinical endocrinology and metabolism 90: 237–246.
[23]
Wu WX, Ma XH, Yoshizato T, Shinozuka N, Nathanielsz PW (1999) Differential expression of myometrial oxytocin receptor and prostaglandin H synthase 2, but not estrogen receptor alpha and heat shock protein 90 messenger ribonucleic acid in the gravid horn and nongravid horn in sheep during betamethasone-induced labor. Endocrinology 140: 5712–5718.
[24]
Liedman R, Hansson SR, Igidbashian S, Akerlund M (2009) Myometrial oxytocin receptor mRNA concentrations at preterm and term delivery – the influence of external oxytocin. Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology 25: 188–193.
[25]
Fuchs AR, Fuchs F, Husslein P, Soloff MS (1984) Oxytocin receptors in the human uterus during pregnancy and parturition. American journal of obstetrics and gynecology 150: 734–741.
[26]
Arrowsmith S, Quenby S, Weeks A, Burdyga T, Wray S (2012) Poor spontaneous and oxytocin-stimulated contractility in human myometrium from postdates pregnancies. PloS one 7: e36787.
[27]
Jie Z, Kendrick A, Quenby S, Wray S (2007) Contractility and calcium signaling of human myometrium are profoundly affected by cholesterol manipulation: implications for labor? Reproductive sciences (Thousand Oaks, Calif) 14: 456–466.
[28]
Wray S (2007) Insights into the uterus. Experimental physiology 92: 621–631.
[29]
Oppenheimer LW, Bland ES, Dabrowski A, Holmes P, McDonald O, et al. (2002) Uterine contraction pattern as a predictor of the mode of delivery. Journal of perinatology: official journal of the California Perinatal Association 22: 149–153.
[30]
Berghella V, Iams JD, Newman RB, Macpherson C, Goldenberg RL, et al. (2004) Frequency of uterine contractions in asymptomatic pregnant women with or without a short cervix on transvaginal ultrasound scan. American journal of obstetrics and gynecology 191: 1253–1256.
[31]
Iams JD, Newman RB, Thom EA, Goldenberg RL, Mueller-Heubach E, et al. (2002) Frequency of uterine contractions and the risk of spontaneous preterm delivery. The New England journal of medicine 346: 250–255.
[32]
Mokgokong ET (1974) The frequency and duration of uterine contractions during labour. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 48: 799–802.
[33]
Bakker PC, Van Rijswijk S, van Geijn HP (2007) Uterine activity monitoring during labor. Journal of perinatal medicine 35: 468–477.
[34]
Tichenor JN, Hansen ET, Buxton IL (2005) Expression of stretch-activated potassium channels in human myometrium. Proceedings of the Western Pharmacology Society 48: 44–48.
[35]
Buxton IL, Heyman N, Wu YY, Barnett S, Ulrich C (2011) A role of stretch-activated potassium currents in the regulation of uterine smooth muscle contraction. Acta pharmacologica Sinica 32: 758–764.
[36]
Monaghan K, Baker SA, Dwyer L, Hatton WC, Sik Park K, et al. (2011) The stretch-dependent potassium channel TREK-1 and its function in murine myometrium. The Journal of physiology 589: 1221–1233.
[37]
Noble K, Floyd R, Shmygol A, Shmygol A, Mobasheri A, et al. (2010) Distribution, expression and functional effects of small conductance Ca-activated potassium (SK) channels in rat myometrium. Cell calcium 47: 47–54.
[38]
Jones K, Shmygol A, Kupittayanant S, Wray S (2004) Electrophysiological characterization and functional importance of calcium-activated chloride channel in rat uterine myocytes. Pflugers Arch 448: 36–43.
[39]
Shynlova O, Mitchell JA, Tsampalieros A, Langille BL, Lye SJ (2004) Progesterone and gravidity differentially regulate expression of extracellular matrix components in the pregnant rat myometrium. Biology of reproduction 70: 986–992.
[40]
Burdyga T, Borisova L, Burdyga AT, Wray S (2009) Temporal and spatial variations in spontaneous Ca events and mechanical activity in pregnant rat myometrium. European journal of obstetrics, gynecology, and reproductive biology 144 Suppl 1S25–32.
[41]
Sokolowski P, Saison F, Giles W, McGrath S, Smith D, et al. (2010) Human uterine wall tension trajectories and the onset of parturition. PloS one 5: e11037.
[42]
Neilson JP, Lavender T, Quenby S, Wray S (2003) Obstructed labour. British medical bulletin 67: 191–204.
