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PIEZO channels link mechanical forces to uterine contractions in parturition

by Yunxiao Zhang, Sejal A. Kini, Sassan A. Mishkanian, Renhao Luo, Saba Heydari Seradj, Verina H. Leung, Yu Wang, M. Rocío Servín-Vences, William T. Keenan, Utku Sonmez, Oleg Yarishkin, Manuel Sanchez-Alavez, Yuejia Liu, Xin Jin, Darren J. Lipomi, Li Ye, Michael Petrascheck, Antonina I. Frolova, Sarah K. England, and Ardem Patapoutian

Posted: September 18, 2025
Server: bioRxiv
DOI: 10.1101/2025.09.17.676899

Abstract

Mechanical forces are extensively involved in pregnancy and parturition, but their precise roles and mechanisms remain poorly understood. Here, we identify mechanically activated ion channels PIEZO1 and PIEZO2 as key mechanotransducers required for labor progression. Genetic deletion of Piezo1 and Piezo2 in mice resulted in weakened uterine contractions and severe parturition defects. Tissue-specific knockouts revealed that deletion in either the uterus or sensory neurons alone caused modest defects, whereas combined loss significantly impaired labor, demonstrating additive effects. Single-nuclei sequencing showed that loss of PIEZO reduced expression of connexin43 (Gja1), a gap junction protein in uterine smooth muscle cells, suggesting a mechanistic link to impaired contraction. These findings highlight the critical role of PIEZO channels in mechanotransduction during parturition and suggest therapeutic targets for labor dysfunction.

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