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

Mar 27, 2018Biochemical pharmacology

Reduced uterine muscle contractions during long-term stretching in full-term and twin pregnancies linked to TREK-1 channel

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Abstract

Prolonged uterine stretch is associated with decreased myometrium contractile activity and enhanced TREK-1 channel activity.

Contractile activity of the myometrium decreases with gestational age and is further reduced in twin pregnancies compared to singleton pregnancies.
Oxytocin-induced contractions are significantly lower in uterine segments exposed to 8 g stretch compared to those under 2 g basal tension.
TREK-1 mRNA and protein levels increase in uterine tissues from singleton term pregnancies compared to singleton preterm pregnancies.
Activation of TREK-1 by arachidonic acid reduces oxytocin contractions in both preterm and term pregnancies.
Blocking TREK-1 with l-methionine enhances oxytocin contractions and reverses the contraction decreases seen in uterine strips under prolonged stretch.

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Quiescence 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 Kchannel (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. +

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

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