The Effects of Prostaglandin E1 and Prostaglandin E2 on in vitro Myometrial Contractility and Uterine Structure

Abstract

Objective To estimate the effects of prostaglandin E1 (PGE1) and E2 (PGE2) on myometrial contractility and structure in vitro.

Study Design Myometrial strips from 18 women were incubated with PGE1 (10⁻⁵ mol/L), PGE2 (10⁻⁵ mol/L), or solvent (CTR) for up to 360 minutes in organ chambers for isometric tension recording. The area under the contraction curve, total collagen content, and percentage of the area covered by connective tissue were calculated at various time periods.

Results PGE1 significantly increased in vitro myometrial contractility up to 90 minutes when compared with PGE2 and CTR (p < 0.01) and up to 180 minutes as compared with PGE2 (p < 0.05). After 360 minutes, CTR and PGE1 samples had lower total collagen content and area covered by connective tissue than PGE2 (p < 0.01).

Conclusion The effects of prostaglandins on the uterus cannot be solely explained by contractility. Treatment with PGE1 significantly increased myometrial contractions and decreased both total collagen content and the area covered by connective tissue. Such findings may explain the higher rates of vaginal delivery, tachysystole, and uterine rupture associated with PGE1 use.

Keywords

prostaglandin E1 - prostaglandin E2 - collagen - uterine contractility - organ chamber

• References

• 1 Martin JA, Hamilton BE, Sutton PD. Births: final data for 2006. National Vital Statistics Reports; Vol. 57, No. 7. Hyattsville, MD: National Center for Health Statistics; 2009
• 2 ACOG Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 107: Induction of labor. Obstet Gynecol 2009; 114 (2 Pt 1) 386-397
• 3 Kelly AJ, Malik S, Smith L, Kavanagh J, Thomas J. Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term. Cochrane Database Syst Rev 2009; (4) CD003101
• 4 Hofmeyr GJ, Gülmezoglu AM, Pileggi C. Vaginal misoprostol for cervical ripening and induction of labour. Cochrane Database Syst Rev 2010; (10) CD000941
• 5 Austin SC, Sanchez-Ramos L, Adair CD. Labor induction with intravaginal misoprostol compared with the dinoprostone vaginal insert: a systematic review and metaanalysis. Am J Obstet Gynecol 2010; 202: 624 , e1–e9
• 6 Vaknin Z, Kurzweil Y, Sherman D. Foley catheter balloon vs locally applied prostaglandins for cervical ripening and labor induction: a systematic review and metaanalysis. Am J Obstet Gynecol 2010; 203: 418-429
• 7 Akhan SE, Iyibozkurt AC, Turfanda A. Unscarred uterine rupture after induction of labor with misoprostol: a case report. Clin Exp Obstet Gynecol 2001; 28: 118-120
• 8 Khabbaz AY, Usta IM, El-Hajj MI, Abu-Musa A, Seoud M, Nassar AH. Rupture of an unscarred uterus with misoprostol induction: case report and review of the literature. J Matern Fetal Med 2001; 10: 141-145
• 9 American College of Obstetricians and Gynecologists. ACOG Practice bulletin No. 115: Vaginal birth after previous cesarean delivery. Obstet Gynecol 2010; 116 (2 Pt 1) 450-463
• 10 Al-Zirqi I, Stray-Pedersen B, Forsén L, Vangen S. Uterine rupture after previous caesarean section. BJOG 2010; 117: 809-820
• 11 Stjernholm YM, Sahlin L, Eriksson HA, Byström BE, Stenlund PM, Ekman GE. Cervical ripening after treatment with prostaglandin E2 or antiprogestin (RU486). Possible mechanisms in relation to gonadal steroids. Eur J Obstet Gynecol Reprod Biol 1999; 84: 83-88
• 12 Ji H, Dailey TL, Long V, Chien EK. Prostaglandin E2-regulated cervical ripening: analysis of proteoglycan expression in the rat cervix. Am J Obstet Gynecol 2008; 198: 536 , e1–e7
• 13 Sahlin L, Stjernholm-Vladic Y, Roos N, Masironi B, Ekman-Ordeberg G. Impaired leukocyte influx in cervix of postterm women not responding to prostaglandin priming. Reprod Biol Endocrinol 2008; 6: 36
• 14 Gordon-Wright AP, Elder MG. Effect of prostaglandin E2 and its metabolites on lower segment myometrium in vitro. Eur J Obstet Gynecol Reprod Biol 1980; 10: 297-302
• 15 Popat A, Crankshaw DJ. Variable responses to prostaglandin E in human non-pregnant myometrium. Eur J Pharmacol 2001; 416: 145-152
• 16 Chiossi G, Costantine MM, Bytautiene E , et al. Misoprostol potentiates spontaneous uterine contractility in vitro. Reprod Sci 2011; 18: 129a
• 17 Edwards CA, O'Brien Jr WD. Modified assay for determination of hydroxyproline in a tissue hydrolyzate. Clin Chim Acta 1980; 104: 161-167
• 18 Woessner Jr JF. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys 1961; 93: 440-447
• 19 Alfirevic Z, Kelly AJ, Dowswell T. Intravenous oxytocin alone for cervical ripening and induction of labour. Cochrane Database Syst Rev 2009; 4: CD003246
• 20 Palliser HK, Hirst JJ, Ooi GT , et al. Prostaglandin e and f receptor expression and myometrial sensitivity at labor onset in the sheep. Biol Reprod 2005; 72: 937-943
• 21 Kronig B. Transperitonealer, cervikaler kaiserschnitt. In: Doderlein A, Kronig B, eds. Operative Gynakologie. 3rd ed. Leipzig, Germany: Georg Thieme; 1912: 870-886
• 22 Buhimschi CS, Zhao G, Sora N, Madri JA, Buhimschi IA. Myometrial wound healing post-Cesarean delivery in the MRL/MpJ mouse model of uterine scarring. Am J Pathol 2010; 177: 197-207
• 23 Buhimschi CS, Buhimschi IA, Yu C , et al. The effect of dystocia and previous cesarean uterine scar on the tensile properties of the lower uterine segment. Am J Obstet Gynecol 2006; 194: 873-883
• 24 Buhimschi CS, Buhimschi IA, Patel S, Malinow AM, Weiner CP. Rupture of the uterine scar during term labour: contractility or biochemistry?. BJOG 2005; 112: 38-42