PIEZO channels link mechanical forces to uterine contractions in parturition

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

doi:10.1126/science.ady3045

PIEZO channels link mechanical forces to uterine contractions in parturition

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Mechanical forces are extensively involved in pregnancy and parturition, but their precise roles and mechanisms remain poorly understood. We identified 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 uterus or sensory neurons alone caused modest defects whereas combined loss markedly impaired labor, demonstrating additive effects. Single-nuclei sequencing indicated that loss of PIEZO function 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.

Original language	English
Article number	eady3045
Journal	Science
Volume	390
Issue number	6774
DOIs	https://doi.org/10.1126/science.ady3045
State	Published - 13 Nov 2025
Externally published	Yes

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Zhang, Y., Kini, S. A., Mishkanian, S. A., Yarishkin, O., Luo, R., Seradj, S. H., Leung, V. H., Wang, Y., Servín-Vences, M. R., Keenan, W. T., Sonmez, U., Sanchez-Alavez, M., Liu, Y., Jin, X., Lipomi, D. J., Ye, L., Petrascheck, M., Frolova, A. I., England, S. K., & Patapoutian, A. (2025). PIEZO channels link mechanical forces to uterine contractions in parturition. Science, 390(6774), Article eady3045. https://doi.org/10.1126/science.ady3045

@article{06c5e62da2594d0ab4c057ec5d9cea7b,

title = "PIEZO channels link mechanical forces to uterine contractions in parturition",

abstract = "Mechanical forces are extensively involved in pregnancy and parturition, but their precise roles and mechanisms remain poorly understood. We identified 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 uterus or sensory neurons alone caused modest defects whereas combined loss markedly impaired labor, demonstrating additive effects. Single-nuclei sequencing indicated that loss of PIEZO function 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.",

author = "Yunxiao Zhang and Kini, \{Sejal A.\} and Mishkanian, \{Sassan A.\} and Oleg Yarishkin and Renhao Luo and Seradj, \{Saba Heydari\} and Leung, \{Verina H.\} and Yu Wang and Serv{\'i}n-Vences, \{M. Roc{\'i}o\} and Keenan, \{William T.\} and Utku Sonmez and Manuel Sanchez-Alavez and Yuejia Liu and Xin Jin and Lipomi, \{Darren J.\} and Li Ye and Michael Petrascheck and Frolova, \{Antonina I.\} and England, \{Sarah K.\} and Ardem Patapoutian",

note = "Publisher Copyright: Copyright {\textcopyright} 2025 the authors, some rights reserved.",

year = "2025",

month = nov,

day = "13",

doi = "10.1126/science.ady3045",

language = "英语",

volume = "390",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6774",

}

Zhang, Y, Kini, SA, Mishkanian, SA, Yarishkin, O, Luo, R, Seradj, SH, Leung, VH, Wang, Y, Servín-Vences, MR, Keenan, WT, Sonmez, U, Sanchez-Alavez, M, Liu, Y, Jin, X, Lipomi, DJ, Ye, L, Petrascheck, M, Frolova, AI, England, SK & Patapoutian, A 2025, 'PIEZO channels link mechanical forces to uterine contractions in parturition', Science, vol. 390, no. 6774, eady3045. https://doi.org/10.1126/science.ady3045

TY - JOUR

T1 - PIEZO channels link mechanical forces to uterine contractions in parturition

AU - Zhang, Yunxiao

AU - Kini, Sejal A.

AU - Mishkanian, Sassan A.

AU - Yarishkin, Oleg

AU - Luo, Renhao

AU - Seradj, Saba Heydari

AU - Leung, Verina H.

AU - Wang, Yu

AU - Servín-Vences, M. Rocío

AU - Keenan, William T.

AU - Sonmez, Utku

AU - Sanchez-Alavez, Manuel

AU - Liu, Yuejia

AU - Jin, Xin

AU - Lipomi, Darren J.

AU - Ye, Li

AU - Petrascheck, Michael

AU - Frolova, Antonina I.

AU - England, Sarah K.

AU - Patapoutian, Ardem

PY - 2025/11/13

Y1 - 2025/11/13

N2 - Mechanical forces are extensively involved in pregnancy and parturition, but their precise roles and mechanisms remain poorly understood. We identified 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 uterus or sensory neurons alone caused modest defects whereas combined loss markedly impaired labor, demonstrating additive effects. Single-nuclei sequencing indicated that loss of PIEZO function 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.

AB - Mechanical forces are extensively involved in pregnancy and parturition, but their precise roles and mechanisms remain poorly understood. We identified 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 uterus or sensory neurons alone caused modest defects whereas combined loss markedly impaired labor, demonstrating additive effects. Single-nuclei sequencing indicated that loss of PIEZO function 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.

UR - https://www.scopus.com/pages/publications/105021725712

U2 - 10.1126/science.ady3045

DO - 10.1126/science.ady3045

M3 - 文章

C2 - 41231991

AN - SCOPUS:105021725712

SN - 0036-8075

VL - 390

JO - Science

JF - Science

IS - 6774

M1 - eady3045

ER -

PIEZO channels link mechanical forces to uterine contractions in parturition

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