PIEZO channels link mechanical forces to uterine contractions in parturition
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 <i>Piezo1</i> and <i>Piezo2</i> 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 (<i>Gja1</i>), 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.
Authors
- Sarah K. England (ORCID: https://orcid.org/0000-0003-4247-0281)
- Verina H. Leung (ORCID: https://orcid.org/0009-0009-3762-7046)
- M. Rocio Servin‐Vences (ORCID: https://orcid.org/0000-0002-7452-9260)
- Renhao Luo (ORCID: https://orcid.org/0000-0003-3489-1799)
- Oleg Yarishkin (ORCID: https://orcid.org/0000-0002-8215-7444)
- William T. Keenan (ORCID: https://orcid.org/0000-0003-3381-744X)
- Manuel Sánchez-Alavez (ORCID: https://orcid.org/0000-0002-8164-8452)
- Utku M. Sönmez
- Yuejia Liu (ORCID: https://orcid.org/0000-0001-9322-5871)
- Sejal A Kini (ORCID: https://orcid.org/0009-0006-6551-9104)
- Ardem Patapoutian
- Yu Wang (ORCID: https://orcid.org/0000-0002-1327-5789)
- Xin Jin (ORCID: https://orcid.org/0000-0003-2344-992X)
- Antonina I. Frolova (ORCID: https://orcid.org/0000-0002-6491-6910)
- Darren J. Lipomi (ORCID: https://orcid.org/0000-0002-5808-7765)
- Michael Petrascheck (ORCID: https://orcid.org/0000-0002-1010-145X)
- Li Ye (ORCID: https://orcid.org/0000-0002-3077-802X)
- Yunxiao Zhang (ORCID: https://orcid.org/0000-0003-2145-4151)
- Saba Heydari Seradj (ORCID: https://orcid.org/0009-0001-8407-6859)
- Sassan A Mishkanian (ORCID: https://orcid.org/0009-0001-7703-0705)
Institutions
- Scripps Research Institute (US)
- Howard Hughes Medical Institute (US)
- Universidad Autónoma de Baja California (MX)
- Washington University in St. Louis (US)
- University of California San Diego (US)
- San Diego Biomedical Research Institute (US)
- Saint Louis University (US)
Publication Details
- Journal
- Science
- Published
- 2025-11-13
- DOI
- https://doi.org/10.1126/science.ady3045
- Citations
- 2
- Primary Topic
- Erythrocyte Function and Pathophysiology
- Type
- article
- Field-Weighted Citation Impact
- 2.33