OBJECTIVE: A novel prostaglandin F2alpha receptor antagonist, THG113.31, was tested for the suppression of uterine contractility and delay of preterm labor in sheep. STUDY DESIGN: We determined the tocolytic effectiveness of THG113.31 on contractions that were stimulated in vitro by prostaglandin F2alpha and E2 in longitudinal and circular myometrial strips. We also tested the ability of THG113.31 in vivo to lower uterine electromyographic activity that was induced by the progesterone receptor blocker, RU486, and to delay preterm birth. RESULTS: THG113.31 suppressed the amplitude of prostaglandin F2alpha, but not prostaglandin E2-induced contractions of both circular and longitudinal myometrium (P<.01). The times to delivery after RU486 were 34.8+/-1.1 hours (saline solution) and 41.9+/-0.5 hours (THG113.31; P<.001) or an average delay of 7.1 hours. There were no changes in fetal blood gases (PaO2 , PaCO2 , pH, or SaO2) because of THG113.31. Fetal cortisol levels rose in each group, and fetal and maternal prostaglandin E2 and F2alpha metabolite concentrations rose similarly in both groups. CONCLUSION: THG113.31 specifically suppresses prostaglandin F2alpha-induced myometrial contractility and delays delivery.
OBJECTIVE: A novel prostaglandin F2alpha receptor antagonist, THG113.31, was tested for the suppression of uterine contractility and delay of preterm labor in sheep. STUDY DESIGN: We determined the tocolytic effectiveness of THG113.31 on contractions that were stimulated in vitro by prostaglandin F2alpha and E2 in longitudinal and circular myometrial strips. We also tested the ability of THG113.31 in vivo to lower uterine electromyographic activity that was induced by the progesterone receptor blocker, RU486, and to delay preterm birth. RESULTS:THG113.31 suppressed the amplitude of prostaglandin F2alpha, but not prostaglandin E2-induced contractions of both circular and longitudinal myometrium (P<.01). The times to delivery after RU486 were 34.8+/-1.1 hours (saline solution) and 41.9+/-0.5 hours (THG113.31; P<.001) or an average delay of 7.1 hours. There were no changes in fetal blood gases (PaO2 , PaCO2 , pH, or SaO2) because of THG113.31. Fetal cortisol levels rose in each group, and fetal and maternal prostaglandin E2 and F2alpha metabolite concentrations rose similarly in both groups. CONCLUSION:THG113.31 specifically suppresses prostaglandin F2alpha-induced myometrial contractility and delays delivery.
Authors: Kelycia B Leimert; Barbara S E Verstraeten; Angela Messer; Rojin Nemati; Kayla Blackadar; Xin Fang; Sarah A Robertson; Sylvain Chemtob; David M Olson Journal: Biol Reprod Date: 2019-05-01 Impact factor: 4.285
Authors: Fiona J Stenning; Graeme R Polglase; Arjan B Te Pas; Kelly J Crossley; Martin Kluckow; Andrew W Gill; Euan M Wallace; Erin V McGillick; Corinna Binder; Douglas A Blank; Calum Roberts; Stuart B Hooper Journal: PLoS One Date: 2021-06-17 Impact factor: 3.240