{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T03:52:27Z","timestamp":1777002747525,"version":"3.51.4"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971335"],"award-info":[{"award-number":["81971335"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Adenomyosis (AM) is traditionally explained by biochemical dysregulation at the endometrial\u2013myometrial interface, leading to passive displacement of endometrial stromal cells (ESCs). However, the uterus is a highly mechanosensitive organ. Aberrant myometrial hypercontractility in AM may expose ESCs to chronic mechanical stimulation. Whether such mechanical cues can modulate ESCs\u2019 behavior under in vitro conditions remains incompletely understood. This study hypothesizes that cyclic mechanical strain\u2014independent of biochemical cues\u2014can induce a pro-migratory and pro-invasive ESC phenotype in vitro. Immortalized human ESCs (hESCs) were subjected to cyclic uniaxial stretching (12% strain, 0.2\u2009Hz, 48\u2009h) to model sustained mechanical loading. We evaluated cellular morphology, migration and invasion (wound healing and Transwell assays), cytoskeletal remodeling (F-actin), extracellular matrix (ECM) related proteins, transcriptomic changes (RNA-sequencing), and MAPK pathway activation. The functional involvement of p38 MAPK was tested using the selective inhibitor Adezmapimod. The results indicated that cyclic stretch induced marked cellular elongation without increasing apoptosis. RNA-sequencing revealed 580 differentially expressed genes enriched in migration and ECM remodeling. Functionally, stretched hESCs exhibited enhanced migration and invasion capacity in vitro, accompanied by elevated F-actin, fibronectin, and CTGF. Mechanistically, mechanical strain triggered selective activation of the p38 MAPK pathway, without affecting ERK or JNK. Pharmacological inhibition of p38 attenuated stretch-associated cytoskeletal remodeling, ECM-related protein expression, and cell motility. Together, these findings demonstrate that cyclic mechanical stretch, as an underexplored non-biochemical factor, can promote a motile and invasive stromal cell phenotype in vitro via a p38 MAPK\/F-actin-associated mechanism. While these results do not establish causality for AM development in vivo, they suggest a potential mechanotransduction pathway through which abnormal uterine mechanics may influence stromal cell behavior. Targeting mechanotransduction\u2014such as p38 inhibition\u2014may represent novel mechano-therapeutics for AM. This warrants further investigation using more complex and physiologically relevant models.<\/jats:p>","DOI":"10.1093\/molehr\/gaag019","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T12:45:18Z","timestamp":1774010718000},"source":"Crossref","is-referenced-by-count":0,"title":["Cyclic stretch activates endometrial stromal cells to enhance migration and invasion via mechanosensitive p38 MAPK and F-actin\n                    <i>in vitro<\/i>"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9995-9565","authenticated-orcid":false,"given":"Yu-Yin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) , Dongguan, Guangdong Province, People's Republic of","place":["China"]},{"name":"Dongguan Key Laboratory of Major Diseases in Obstetrics and Gynecology , Dongguan, Guangdong Province, People's Republic of","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2307-4393","authenticated-orcid":false,"given":"Yu-Hang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) , Dongguan, Guangdong Province, People's Republic of","place":["China"]},{"name":"Dongguan Key Laboratory of Major Diseases in Obstetrics and Gynecology , Dongguan, Guangdong Province, People's Republic of","place":["China"]},{"name":"The First School of Clinical Medicine, Guangdong Medical University , Zhanjiang, Guangdong Province, People's Republic of","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2703-0949","authenticated-orcid":false,"given":"Chu-Jun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) , Dongguan, Guangdong Province, People's Republic of","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2908-7990","authenticated-orcid":false,"given":"Xue-Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) , Dongguan, Guangdong Province, People's Republic of","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5018-9606","authenticated-orcid":false,"given":"Shu-Lin","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) , Dongguan, Guangdong Province, People's Republic of","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7282-7380","authenticated-orcid":false,"given":"Shu-Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) , Dongguan, Guangdong Province, People's Republic of","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4076-7536","authenticated-orcid":false,"given":"Ming-Xiu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital) , Dongguan, Guangdong Province, People's Republic of","place":["China"]},{"name":"Dongguan Key Laboratory of Major Diseases in Obstetrics and Gynecology , Dongguan, Guangdong Province, People's Republic 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