K_V7 channel activation inhibits human and murine myometrium contractility and delays delivery in a mouse model of preterm birth.

Authors

Yosef T Mansour, Hiten D Mistry, Evonne C Chin-Smith, Mariola K Zaleska, Deanna C Sekulich, Jennifer L Herington, Jeff Reese, Rima Patel, Philip I Aaronson, Donna M Slater, Sarah K England, Iain A Greenwood, Mark R Johnson, Paul D Taylor, Rachel M Tribe

Published in

Communications medicine. Volume 6. Issue 1. Sep 03, 2026. Epub Sep 03, 2026.

Abstract

Spontaneous preterm birth, defined as delivery before 37 weeks of gestation, remains a global cause of neonatal illness and death, yet treatments for preterm labor remain limited. We hypothesized that K_V7 channels in the uterus (myometrium), could be a therapeutic target for preventing or treating preterm labor. The aim was to characterize K_V7 channel subtypes in human myometrium present after labor onset, and to use a preterm birth mouse model to provide proof-of-principal evidence that activating these channels in vivo can delay preterm delivery.
This experimental study integrated studies of human myometrial tissue (term and preterm pregnancies, n = 159 across experiments), with a RU486-induced preterm birth mouse model (C57BL/6 J, n = 6-9 per experimental group), and ex vivo fetal ductus arteriosus preparations (CD-1 mice, n = 10 per group). Molecular and protein profiling, isometric tension recordings, and functional pharmacology were used to characterize K_V7 mediated regulation of human and mouse uterine contractility. In vivo dosing studies in mice assessed the effects of K_V7 activators (retigabine and ML213) on delivery timing (n = 6-9).
We show that K_V7 channels and ancillary units (KCNE1-5), are expressed in pregnant human myometrium, prior to and after the onset of labor. KCNQ4 and KCNE4 transcripts are also present in myometrium taken at preterm gestations ( ± labor). K_V7.2-5 activators markedly reduce spontaneous contractions in human and mouse myometrium in vitro and significantly delay preterm birth in vivo with limited impact on fetal ductus arteriosus function.
These findings support K_V7 activation as a promising approach to suppress uterine contractility and hence delay preterm birth, highlighting a potential new direction for either drug repurposing or therapeutic development.

PMID:
42693196
Bibliographic data and abstract were imported from PubMed on 04 Sep 2026.

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