{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:52:24Z","timestamp":1788587544036,"version":"build-2803163510"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T00:00:00Z","timestamp":1693958400000},"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":["81960280"],"award-info":[{"award-number":["81960280"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012547","name":"Natural Science Foundation of Guangxi Zhuang Autonomous Region","doi-asserted-by":"publisher","award":["2018GXNSFAA050136"],"award-info":[{"award-number":["2018GXNSFAA050136"]}],"id":[{"id":"10.13039\/100012547","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Intrauterine adhesions (IUA) are a common gynecological problem. Stem cell therapy has been widely used in the treatment of IUA. However, due to the complex and harsh microenvironment of the uterine cavity, the effectiveness of such therapy is greatly inhibited. This study aimed to investigate whether melatonin pretreatment enhances the efficacy of human umbilical cord mesenchymal stem cells (HucMSCs) in IUA treatment in rats. First, we explored the effect of melatonin on the biological activity of HucMSCs in vitro through a macrophage co-culture system, Cell Counting Kit 8 (CCK-8), 5-Ethynyl-2\u2032-deoxyuridine (EdU), flow cytometry, immunofluorescence staining, and qRT-PCR. Subsequently, we established the IUA rat model and tracked the distribution of HucMSCs in this model. In addition, we observed the number of M1 and M2 macrophages through immunofluorescence staining and detected the levels of inflammatory cytokines. Four weeks after cell transplantation, HE, Masson, and immunohistochemical staining were performed. In vitro experiments showed that melatonin pretreatment of HucMSCs promoted proliferation, reduced apoptosis, up-regulated the stemness gene, and regulated macrophage polarization. In vivo, melatonin pretreatment caused more HucMSCs to remain in the uterine cavity. Melatonin-pretreated HucMSCs recruited more macrophages, regulated macrophage polarization, and reduced inflammation. Melatonin-pretreated HucMSCs relieved fibrosis, increased endometrium thickness, and up-regulated CD34, vimentin, proliferating cell nuclear antigen (PCNA), and alpha small muscle antigen (\u03b1-SMA) expression. Fertility tests showed that melatonin-pretreated HucMSCs increased the number of embryos. In summary, pretreatment with melatonin was beneficial for HucMSC treatment because it enhanced the cell\u2019s ability to recruit macrophages and regulate macrophage polarization, which led to the regeneration of the endometrium and improved pregnancy outcomes.<\/jats:p>","DOI":"10.1093\/biolre\/ioad102","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T15:20:26Z","timestamp":1694013626000},"page":"918-937","source":"Crossref","is-referenced-by-count":15,"title":["Melatonin-pretreated human umbilical cord mesenchymal stem cells improved endometrium regeneration and fertility recovery through macrophage immunomodulation in rats with intrauterine adhesions"],"prefix":"10.1093","volume":"109","author":[{"given":"Weili","family":"Qin","sequence":"first","affiliation":[{"name":"Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University , Nanning , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Wang","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University , Nanning , China"},{"name":"Reproductive and Genetic Hospital , The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, , Hefei , China"},{"name":"University of Science and Technology of China , The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, , Hefei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianwen","family":"Hu","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University , Nanning , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongyan","family":"Qin","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University , Nanning , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Ma","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University , Nanning , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengque","family":"Zheng","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University , Nanning , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencai","family":"Tian","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University , Nanning , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University , Nanning , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Li","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University , Nanning , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufu","family":"Jin","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University , Nanning , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liao","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University , Nanning , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Qin","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University , Nanning , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,6]]},"reference":[{"key":"2024010817191541300_ref1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.fertnstert.2008.02.096","article-title":"Asherman syndrome--one century later","volume":"89","author":"Yu","year":"2008","journal-title":"Fertil Steril"},{"key":"2024010817191541300_ref2","doi-asserted-by":"crossref","first-page":"5175","DOI":"10.3390\/ijms22105175","article-title":"Focus on the primary prevention of intrauterine adhesions: current concept and vision","volume":"22","author":"Lee","year":"2021","journal-title":"Int J Mol 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