{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T19:15:21Z","timestamp":1788894921095,"version":"build-2803163510"},"reference-count":67,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"publisher","award":["M808"],"award-info":[{"award-number":["M808"]}],"id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>We examined the role of myofibroblasts in regulating Cx43 and collagen structure in iatrogenic preterm amniotic membrane (AM) defects subjected to mechanical stimulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Preterm AM specimens were collected from women undergoing planned preterm caesarean section after in utero intervention for correction of spina bifida by open fetal surgery (<jats:italic>n<\/jats:italic>\u00a0=\u00a04 patients; preterm delivery at 34\u00a0+\u00a00\u00a0weeks to 35\u00a0+\u00a00\u00a0weeks). Control specimens taken 5\u00a0cm away from the open fetal surgery defect site were compared with wound edge AM. In separate experiments, the effects of mechanical stimulation and co\u2010treatment with Cx43 antisense on matrix and repair proteins were examined. Specimens were immunostained to detect \u03b1SMA and Cx43 in myofibroblasts and counterstained with DAPI to quantify nuclei shape. The direction of collagen fibrils in the wound edge region was examined by SHG imaging. Markers for matrix (collagen, elastin, GAG), inflammation (PGE<jats:sub>2<\/jats:sub>) and repair (TGF\u03b2<jats:sub>1<\/jats:sub>) were examined by RT\u2010qPCR and biochemical assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In iatrogenic preterm AM specimens, the diameter of the open fetal surgery defect ranged between 3.5 and 7.5\u00a0cm. At the wound edge of the open fetal surgery defect, \u03b1SMA positive myofibroblasts had deformed nuclei and showed abundant Cx43 localized in the cell bodies or formed plaques. In the fibroblast layer, collagen had degenerated in some regions or had polarity near the wound edge. In preterm AM defects, mechanical stimulation and Cx43 antisense increased the levels of collagen and elastin but not GAG or PGE<jats:sub>2<\/jats:sub> release. Mechanical stimulation increased Cx43 and TGF\u03b2<jats:sub>1<\/jats:sub> gene expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In open fetal surgery defects, myofibroblasts were elongated with collagen fibrils that either degenerated or had polarity. Whilst cells produced substantially higher Cx43 in the fibroblast than in the epithelial layer, they formed plaques, which may prevent migration and delay healing. Mechanical stimulation of preterm AM enhanced matrix repair proteins and the mechanotransduction should be explored to understand how Cx43 contributes to membrane integrity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pd.6722","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T01:29:37Z","timestamp":1733362177000},"page":"102-112","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Role of Myofibroblasts in the Repair of Iatrogenic Preterm Membranes Subjected to Mechanical Stimulation"],"prefix":"10.1002","volume":"45","author":[{"given":"E.","family":"Costa","sequence":"first","affiliation":[{"name":"Centre for Bioengineering School of Engineering and Materials Science Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Thrasivoulou","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. L.","family":"Becker","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4920-945X","authenticated-orcid":false,"given":"J.","family":"Deprest","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University Hospitals Leuven  Leuven Belgium"},{"name":"EGA Institute for Women's Health University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0199-6140","authenticated-orcid":false,"given":"A. L.","family":"David","sequence":"additional","affiliation":[{"name":"EGA Institute for Women's Health University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4167-7782","authenticated-orcid":false,"given":"T. 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