{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T03:10:18Z","timestamp":1789269018267,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006510","name":"Duke University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006510","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1HD092316"],"award-info":[{"award-number":["RO1HD092316"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23HD115837"],"award-info":[{"award-number":["K23HD115837"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015521","name":"Stanford Maternal and Child Health Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015521","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"\n Abstract<\/jats:title>\n \n Understanding the mechanism of oxytocin\u2010induced uterine contractility is critical for addressing conditions at both extremes of the uterine contractility spectrum, preterm labour and uterine atony. We hypothesized that oxytocin induces extracellular calcium influx and uterine contraction through activation of the transient receptor potential vanilloid 4 (TRPV4) channel. To test this hypothesis, uterine tissue was obtained with informed consent from pregnant patients undergoing term, non\u2010labouring caesarean delivery. In human myometrial tissue and smooth muscle cells in primary culture (mSMCs), TRPV4 and oxytocin receptor (OXTR) proteins colocalize at distances less than 40\u00a0nm. In mSMCs, both pharmacological blockade of TRPV4 and TRPV4 depletion via small interfering RNA prevent oxytocin\u2010induced calcium influx and contraction. In contrast, voltage\u2010gated calcium channel blockade does not diminish oxytocin\u2010induced calcium transients. Pharmacological blockade of OXTR has no effect on TRPV4 agonist\u2010induced calcium influx or contractility. In uterine tissue from patients with oxytocin\u2010resistant uterine atony, there is a marked reduction in glycosylated OXTR expression and in proximity ligation between OXTR and TRPV4 compared with tissue from control patients with optimal postpartum contractility. Taken together, these findings demonstrate that in the gravid uterine smooth muscle, TRPV4 activation is required for oxytocin\u2010induced uterine contraction. They also suggest reduced OXTR\u2013TRPV4 protein\u2013protein interaction as a novel pathophysiological mechanism underlying uterine atony in non\u2010labouring parturients. These findings highlight the physiological importance of oxytocin signalling via the TRPV4 channel and may motivate the development of targeted, TRPV4\u2010focused treatments to modulate uterine contractility.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Oxytocin\u2010induced contraction in smooth muscle cells from term pregnant human myometrium requires activation of the TRPV4 calcium channel.<\/jats:p>\n <\/jats:list-item>\n \n TRPV4 and oxytocin receptor (OXTR) colocalize at <40\u00a0nM and interact functionally in myometrial smooth muscle cells.<\/jats:p>\n <\/jats:list-item>\n \n TRPV4 antagonism or siRNA\u2010mediated TRPV4 knockdown abolishes oxytocin\u2010induced calcium influx and contractility.<\/jats:p>\n <\/jats:list-item>\n \n In patients with oxytocin\u2010resistant uterine atony, glycosylated OXTR quantity and TRPV4\u2013OXTR colocalization are markedly reduced.<\/jats:p>\n <\/jats:list-item>\n \n These findings identify TRPV4 as a critical mediator of uterine contractility.<\/jats:p>\n <\/jats:list-item>\n \n TRPV4 antagonists may have a role as novel therapeutic agents for preventing or treating preterm labour.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp289262","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:59:17Z","timestamp":1772989157000},"page":"3135-3158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In the gravid human uterus, oxytocin induces smooth muscle cell contraction via transient receptor potential vanilloid 4 channel activation"],"prefix":"10.1113","volume":"604","author":[{"given":"Daiana","family":"Fornes","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Asthma, and Sleep Medicine, Department of Pediatrics Stanford University School of Medicine Stanford California USA"},{"name":"Center for Excellence in Pulmonary Biology, Department of Pediatrics Stanford University School of Medicine Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica R.","family":"Ansari","sequence":"additional","affiliation":[{"name":"Division of Obstetric Anesthesiology and Maternal Health, Department of Anesthesiology, Perioperative and Pain Medicine Stanford University School of Medicine Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermina","family":"Michel","sequence":"additional","affiliation":[{"name":"Division of Obstetric Anesthesiology and Maternal Health, Department of Anesthesiology, Perioperative and Pain Medicine Stanford University School of Medicine Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina M.","family":"Alvira","sequence":"additional","affiliation":[{"name":"Division of Critical Care Medicine, Department of Pediatrics University of California San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N.","family":"Cornfield","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Asthma, and Sleep Medicine, Department of Pediatrics Stanford University School of Medicine Stanford California USA"},{"name":"Center for Excellence in Pulmonary Biology, Department of Pediatrics Stanford University School of Medicine Stanford California 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