{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:51:35Z","timestamp":1793314295687,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T00:00:00Z","timestamp":1731715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515011821"],"award-info":[{"award-number":["2024A1515011821"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515140168"],"award-info":[{"award-number":["2023A1515140168"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2024,11,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Breast cancer patients have high serum reactive oxygen species (ROS) levels, which exert toxicity on the ovary. However, it is still unclear whether tumor\u2010derived ROS play a role in endometrial development and function in breast cancer. Breast cancer patients and healthy controls were recruited and endometrial thickness was measured by transvaginal ultrasound (TVUS). Xenograft tumors of the breast cancer cell line MDA\u2013MB\u2013231 in a female BALB\/c nude mice model were established, and the therapeutic mechanism of vitamin C (VC) was investigated on uterine pathology in\u00a0vivo and the contribution of co\u2010culture of breast cancer cell and endometrial epithelial cell on this process was examined in\u00a0vitro. Median thickness in endometria was lower in breast cancer patients and tumor\u2010bearing mice compared to controls. A gene signature of uteri in tumor\u2010bearing mice demonstrated differential expression of genes (DEGs) regulating extracellular matrix (ECM) and epithelial\u2013mesenchymal transition (EMT), and activation of TGF\u2010\u03b2 and MAPK signaling pathways. In addition, ROS, EMT\u2010 and ECM\u2010related protein levels were enhanced in uteri in tumor\u2010bearing mice, as well as in Ishikawa cells which were co\u2010cultured with MDA\u2010MB\u2010231 cells compared to controls. Supplementation with VC reduced endometrial damage, inhibited the EMT process and collagen deposition, and maintained better histologic architecture of uteri in tumor\u2010bearing mice via inactivation of the TGF\u2010\u03b21\/p38MAPK pathway. In women with breast cancer oxidative stress in the endometrium results in a fibrotic response as a consequence of EMT. VC could alleviate endometrial fibrosis via TGF\u2010\u03b21\/p38MAPK pathway and provide new predictive and therapeutic targets for fertility preservation in younger breast cancer patients.<\/jats:p>","DOI":"10.1096\/fj.202401257rr","type":"journal-article","created":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T08:02:49Z","timestamp":1731744169000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Oxidative stress drives endometrial fibrosis via TGF\u2010\u03b21\/MAPK signaling pathway in breast cancer"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4236-0346","authenticated-orcid":false,"given":"Hui","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pathology Jinan University School of Medicine  Guangzhou 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