{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:29:50Z","timestamp":1792042190091,"version":"4.4.0"},"reference-count":59,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"10","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,3,7]]},"abstract":"<jats:p>Preterm birth is detrimental to the well-being of both the mother and the newborn. During normal gestation, the myometrium is maintained in a quiescent state by progesterone. As a steroid hormone, progesterone is thought to modify uterine and placental morphology by altering gene expression, but another direct mode of action has long been suspected. Here, we reveal the nongenomic molecular mechanism of progesterone as the activation of human and murine inwardly rectifying potassium channel Kir7.1, which is expressed in myometrium and placental pericytes during late gestation. Kir7.1 is also activated by selective steroids, including those used to prevent premature labor, such as 17-\u03b1-hydroxyprogesterone caproate and dydrogesterone, revealing their unexpected mode of action. Our results reveal that Kir7.1 is the molecular target of both endogenous and synthetic steroids that control uterine excitability and placental function. Kir7.1, therefore, is a promising therapeutic target to support healthy pregnancy during mid and late gestation.<\/jats:p>","DOI":"10.1126\/sciadv.adr5086","type":"journal-article","created":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T13:58:51Z","timestamp":1741183131000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Kir7.1 is the physiological target for hormones and steroids that regulate uteroplacental function"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8886-8773","authenticated-orcid":true,"given":"Monika","family":"Haoui","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7388-4278","authenticated-orcid":true,"given":"Citlalli","family":"Vergara","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA."},{"name":"Center for the Investigation of Membrane Excitability Diseases (CIMED), WashU Medicine; Washington University in St. Louis, School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6738-2221","authenticated-orcid":true,"given":"Lina","family":"Kenzler","sequence":"additional","affiliation":[{"name":"Department of Chemosensation, Institute for Biology II, RWTH Aachen University, 52074 Aachen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8753-5732","authenticated-orcid":true,"given":"Jerome","family":"Schr\u00f6er","sequence":"additional","affiliation":[{"name":"Department of Chemosensation, Institute for Biology II, RWTH Aachen University, 52074 Aachen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8894-8079","authenticated-orcid":true,"given":"Geraldine","family":"Zimmer-Bensch","sequence":"additional","affiliation":[{"name":"Department of Neuroepigenetics, Institute for Biology II, RWTH Aachen University, 52074 Aachen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6692-2388","authenticated-orcid":true,"given":"David","family":"Fleck","sequence":"additional","affiliation":[{"name":"Department of Chemosensation, Institute for Biology II, RWTH Aachen University, 52074 Aachen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0336-5798","authenticated-orcid":true,"given":"Christopher","family":"Wiesbrock","sequence":"additional","affiliation":[{"name":"Department of Chemosensation, Institute for Biology II, RWTH Aachen University, 52074 Aachen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6616-4196","authenticated-orcid":true,"given":"Marc","family":"Spehr","sequence":"additional","affiliation":[{"name":"Department of Chemosensation, Institute for Biology II, RWTH Aachen University, 52074 Aachen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3140-2769","authenticated-orcid":true,"given":"Polina V.","family":"Lishko","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA."},{"name":"Center for the Investigation of Membrane Excitability Diseases (CIMED), WashU Medicine; Washington University in St. Louis, School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"What is the strongest muscle in the human body (2019\/updated 2024); www.loc.gov\/everyday-mysteries\/biology-and-human-anatomy\/item\/what-is-the-strongest-muscle-in-the-human-body\/."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-032420-035509"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2008.01665.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(84)90428-9"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-2115(02)00422-0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00019.2023"},{"key":"e_1_3_2_8_2","unstructured":"S. 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