{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T11:22:29Z","timestamp":1781090549631,"version":"3.54.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R21 HD110610"],"award-info":[{"award-number":["R21 HD110610"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01 HD037831"],"award-info":[{"award-number":["R01 HD037831"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Labor dystocia occurs in 21% of deliveries, increasing the risk of adverse maternal and neonatal outcomes. Pregnant women with obesity have an increased prevalence of labor dystocia due to reduced myometrial contractility. Similarly, in a mouse model, diet-induced obesity (DIO) led to reduced uterine contractility and dystocia, although the underlying mechanisms are not fully understood. Here, we focused on the KATP channel, which links metabolic changes to cellular excitability. KATP channels are activated by a decrease in intracellular adenosine triphosphate\/adenosine diphosphate (ATP\/ADP) ratio, resulting in cell membrane hyperpolarization and cytoprotection. We show that myometrial smooth muscle cells (MSMCs) isolated from DIO mice had lower mean KATP currents than MSMCs from control-diet (CON) mice. KATP channel blockade by glibenclamide significantly reduced the ex vivo frequency of contractility in uterine tissue from CON mice but not in tissue from DIO mice, suggesting reduced KATP channel activity in DIO mice. Expression of the KATP subunits Kir6.1 and Sur2 was similar between uterine tissues from CON and DIO mice. Analysis of metabolomics data revealed that uterine tissue from DIO mice had a higher ATP\/ADP ratio and lower quantities of several phosphatidylinositols than tissue from CON mice. Finally, MSMCs from DIO mice had fewer caveolae and less colocalization of Kir6.1 and caveolin 1 than MSMCs from CON mice. Our results suggest that reduced myometrial KATP channel activity contributes to dampened uterine contractility in obese pregnant mice.<\/jats:p>","DOI":"10.1093\/biolre\/ioaf130","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T08:18:45Z","timestamp":1749802725000},"page":"615-625","source":"Crossref","is-referenced-by-count":2,"title":["Myometrial smooth muscle KATP channel activity is attenuated in a mouse model of diet-induced obesity during pregnancy"],"prefix":"10.1093","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9506-117X","authenticated-orcid":false,"given":"Tsuyoshi","family":"Murata","sequence":"first","affiliation":[{"name":"Center for Reproductive Health Sciences, Department of Obstetrics and Gynecology, WashU Medicine , 425 South Euclid Avenue, Campus Box 8064, St. Louis, Missouri 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8411-9997","authenticated-orcid":false,"given":"Kevin K","family":"Prifti","sequence":"additional","affiliation":[{"name":"Center for Reproductive Health Sciences, Department of Obstetrics and Gynecology, WashU Medicine , 425 South Euclid Avenue, Campus Box 8064, St. Louis, Missouri 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8202-9840","authenticated-orcid":false,"given":"Xiaofeng","family":"Ma","sequence":"additional","affiliation":[{"name":"Center for Reproductive Health Sciences, Department of Obstetrics and Gynecology, WashU Medicine , 425 South Euclid Avenue, Campus Box 8064, St. Louis, Missouri 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4990-8477","authenticated-orcid":false,"given":"Lindsey N","family":"Kent","sequence":"additional","affiliation":[{"name":"Center for Reproductive Health Sciences, Department of Obstetrics and Gynecology, WashU Medicine , 425 South Euclid Avenue, Campus Box 8064, St. Louis, Missouri 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6491-6910","authenticated-orcid":false,"given":"Antonina I","family":"Frolova","sequence":"additional","affiliation":[{"name":"Center for Reproductive Health Sciences, Department of Obstetrics and Gynecology, WashU Medicine , 425 South Euclid Avenue, Campus Box 8064, St. Louis, Missouri 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4247-0281","authenticated-orcid":false,"given":"Sarah K","family":"England","sequence":"additional","affiliation":[{"name":"Center for Reproductive Health Sciences, Department of Obstetrics and Gynecology, WashU Medicine , 425 South Euclid Avenue, Campus Box 8064, St. Louis, Missouri 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"2025091917105336800_ref1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ajog.2014.01.026","article-title":"Safe prevention of the primary cesarean delivery","volume":"210","author":"Caughey","year":"2014","journal-title":"Am J Obstet Gynecol"},{"key":"2025091917105336800_ref2","doi-asserted-by":"crossref","first-page":"S1104","DOI":"10.1016\/j.ajog.2022.10.011","article-title":"Dysfunctional labor and delivery: adverse effects on offspring","volume":"228","author":"Friedman","year":"2023","journal-title":"Am J Obstet Gynecol"},{"key":"2025091917105336800_ref3","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/j.1471-0528.2006.01233.x","article-title":"Poor uterine contractility in obese 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