{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T09:56:14Z","timestamp":1781690174308,"version":"3.54.5"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:00:00Z","timestamp":1768003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Research Initiation Fund of Longgang District Maternity & Child Healthcare Hospital of Shenzhen City","award":["Y2024002"],"award-info":[{"award-number":["Y2024002"]}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"publisher","award":["2023A1515010112"],"award-info":[{"award-number":["2023A1515010112"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471717"],"award-info":[{"award-number":["82471717"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cervical insufficiency (CI) affects 0.1%\u20132% of pregnancies and represents a significant cause of second-trimester pregnancy loss and preterm birth; yet, its pathophysiology remains incompletely understood. This study investigated whether aquaporin-3 (AQP3) facilitates hydrogen peroxide (H\u2082O\u2082) transport into cervical macrophages, driving their polarization toward a pro-inflammatory phenotype and subsequent cervical matrix degradation. Cervical tissues from women with CI demonstrated 1.45-fold higher AQP3 expression compared to gestational age-matched controls, with increased colocalization with macrophages. Tissue H\u2082O\u2082 levels were elevated 2.43-fold in CI, accompanied by increased oxidative damage markers and reduced collagen content. In vitro studies using THP-1 macrophages revealed that AQP3 knockdown prevented intracellular H\u2082O\u2082 accumulation despite pro-inflammatory stimulation, blocking M1 polarization and NF-\u03baB activation. Co-culture experiments demonstrated that AQP3-dependent M1 macrophages increased matrix metalloproteinase (MMP)-9 activity 3.8-fold and reduced fibroblast collagen content by 59%. Both H\u2082O\u2082 scavenging with PEG-catalase and NF-\u03baB inhibition with Bay 11-7082 prevented macrophage-mediated matrix degradation. These findings suggest that AQP3 may serve as an important mediator linking oxidative stress to inflammatory cervical remodeling through facilitation of H\u2082O\u2082 influx, NF-\u03baB activation, and M1 macrophage polarization. Targeting AQP3 or its downstream signaling may represent a potential therapeutic approach that requires preclinical validation to prevent CI-associated pregnancy complications.<\/jats:p>","DOI":"10.1093\/biolre\/ioag009","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T12:49:01Z","timestamp":1767962941000},"page":"1967-1979","source":"Crossref","is-referenced-by-count":0,"title":["AQP3-mediated H\u2082O\u2082 transport drives macrophage M1 polarization and cervical matrix remodeling in cervical insufficiency"],"prefix":"10.1093","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2573-4393","authenticated-orcid":false,"given":"Hanbo","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Longgang District Maternity and Child Healthcare Hospital of Shenzhen City, Longgang Maternity and Child Institute of Shantou University Medical College, Shenzhen, Guangdong ,","place":["China"]},{"name":"Medical Research Institute of Maternal and Child, Longgang Maternity and Child Institute of Shantou University Medical College, Longgang District Maternity and Child Healthcare Hospital of Shenzhen City , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Longgang District Maternity and Child Healthcare Hospital of Shenzhen City, Longgang Maternity and Child Institute of Shantou University Medical College , Shenzhen, Guangdong ,","place":["China"]},{"name":"Medical Research Institute of Maternal and Child, Longgang Maternity and Child Institute of Shantou University Medical College, Longgang District Maternity and Child Healthcare Hospital of Shenzhen City , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Long","sequence":"additional","affiliation":[{"name":"Medical Research Institute of Maternal and Child, Longgang Maternity and Child Institute of Shantou University Medical College, Longgang District Maternity and Child Healthcare Hospital of Shenzhen City , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuju","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Research Institute of Maternal and Child, Longgang Maternity and Child Institute of Shantou University Medical College, Longgang District Maternity and Child Healthcare Hospital of Shenzhen City , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danling","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Longgang District Maternity and Child Healthcare Hospital of Shenzhen City, Longgang Maternity and Child Institute of Shantou University Medical College , Shenzhen, Guangdong 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