• Biochemical pharmacology · Jun 2018

    Adaptive reduction of human myometrium contractile activity in response to prolonged uterine stretch during term and twin pregnancy. Role of TREK-1 channel.

    • Zongzhi Yin, Wenzhu He, Yun Li, Dan Li, Hongyan Li, Yuanyuan Yang, Zhaolian Wei, Bing Shen, Xi Wang, Yunxia Cao, and Raouf A Khalil.
    • Department of Obstetrics and Gynecology, Anhui Medical University, Hefei, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, The First Affiliated Hospital, Anhui Medical University, Hefei, China.
    • Biochem. Pharmacol. 2018 Jun 1; 152: 252-263.

    AbstractQuiescence of myometrium contractile activity allows uterine expansion to accommodate the growing fetus and prevents preterm labor particularly during excessive uterine stretch in multiple pregnancy. However, the mechanisms regulating uterine response to stretch are unclear. We tested the hypothesis that prolonged uterine stretch is associated with decreased myometrium contractile activity via activation of TWIK-related K+ channel (TREK-1). Pregnant women at different gestational age (preterm and term) and uterine stretch (singleton and twin pregnancy) were studied, and uterine strips were isolated for measurement of contractile activity and TREK-1 channel expression/activity. Both oxytocin- and KCl-induced contraction were reduced in term vs preterm pregnancy and in twin vs singleton pregnancy. Oxytocin contraction was reduced in uterine segments exposed to 8 g stretch compared to control tissues under 2 g basal tension. TREK-1 mRNA expression and protein levels were augmented in Singleton-Term vs Singleton-Preterm, and in uterine strips exposed to 8 g stretch. The TREK-1 activator arachidonic acid reduced oxytocin contraction in preterm and term, singleton and twin pregnant uterus. The TREK-1 blocker l-methionine enhanced oxytocin contraction in Singleton-Term and twin pregnant uterus, and reversed the decreases in contraction in uterine strips exposed to prolonged stretch. Carboprost-induced uterine contraction was also reduced by arachidonic acid and enhanced by l-methionine. Thus, myometrium contraction decreases with gestational age and uterine expansion in twin pregnancy. The results suggest that prolonged stretch enhances the expression/activity of TREK-1 channel, leading to decreased myometrium contractile activity and maintained healthy term pregnancy particularly in multiple pregnancy.Copyright © 2018 Elsevier Inc. All rights reserved.

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