PMID- 37801891 OWN - NLM STAT- MEDLINE DCOM- 20231206 LR - 20231228 IS - 1872-7603 (Electronic) IS - 0165-0378 (Linking) VI - 160 DP - 2023 Dec TI - Granulocyte-macrophage colony-stimulating factor promotes endometrial repair after injury by regulating macrophages in mice. PG - 104156 LID - S0165-0378(23)00362-5 [pii] LID - 10.1016/j.jri.2023.104156 [doi] AB - Intrauterine adhesion (IUA) caused by endometrial injury is a common cause of female infertility and is challenging to treat. Macrophages play a critical role in tissue repair and cyclical endometrial regeneration. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has significant reparative and anti-fibrotic effects in various tissues. However, there is limited research on the role of GM-CSF in the repair of endometrial injury and the involvement of macrophages in GM-CSF-mediated endometrial repair. In this study, using a mouse model of endometrial scratching injury, we found that GM-CSF treatment accelerated the repair of endometrial injury and improved fertility. At the molecular level, we observed that GM-CSF can downregulate the transcript levels of tumor necrosis factor (TNF) in mouse bone marrow-derived macrophages (BMDMs) stimulated by lipopolysaccharide (LPS) and upregulate the expression of Arginase-1 (Arg-1) and mannose receptor C-type 1 (MRC1). Importantly, during the early and middle stages of injury, GM-CSF increased the proportion of M1-like, M2-like, and M1/M2 mixed macrophages, while in the late stage of injury, GM-CSF facilitated a decline in the number of M2-like macrophages. These findings suggest that GM-CSF may promote endometrial repair by recruiting macrophages and modulating the LPS-induced M1-like macrophages into a less inflammatory phenotype. These insights have the potential to contribute to the development of novel therapeutic approaches for the treatment of intrauterine adhesion and related infertility. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Zhu, Xiaohong AU - Zhu X AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou 310016, China; Department of Obstetrics and Gynecology, Affiliated Xiaoshan Hospital, Hangzhou Normal University (Zhejiang Xiaoshan Hospital), 311201 Hangzhou, China. FAU - Chen, Sijia AU - Chen S AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou 310016, China. FAU - Zhang, Peipei AU - Zhang P AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou 310016, China; Department of Obstetrics and Gynecology, Tiantai People's Hospital of Zhejiang Province, 317200 Taizhou, China. FAU - Ma, Yana AU - Ma Y AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou 310016, China. FAU - Liu, Xiu AU - Liu X AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou 310016, China; Key Laboratory of Reproductive Dysfunction, Management of Zhejiang Province, 310016 Hangzhou, China. FAU - Fei, Haiyi AU - Fei H AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou 310016, China; Key Laboratory of Reproductive Dysfunction, Management of Zhejiang Province, 310016 Hangzhou, China. FAU - Qian, Jingjing AU - Qian J AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou 310016, China; Department of Obstetrics and Gynecology, Yuyao People's Hospital, 315400 Ningbo, China. FAU - Hao, Yanqing AU - Hao Y AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou 310016, China. FAU - Jiang, Lingling AU - Jiang L AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou 310016, China; Key Laboratory of Reproductive Dysfunction, Management of Zhejiang Province, 310016 Hangzhou, China. Electronic address: linglingjiang@zju.edu.cn. FAU - Lin, Xiaona AU - Lin X AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Jianggan District, Hangzhou 310016, China; Key Laboratory of Reproductive Dysfunction, Management of Zhejiang Province, 310016 Hangzhou, China. Electronic address: linna73@zju.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230923 PL - Ireland TA - J Reprod Immunol JT - Journal of reproductive immunology JID - 8001906 RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Female MH - *Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology MH - Lipopolysaccharides/pharmacology MH - *Macrophages/metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - *Endometrium/injuries MH - Animals MH - Mice OTO - NOTNLM OT - Endometrial injury OT - Fibrosis OT - GM-CSF OT - Intrauterine adhesion OT - Macrophages COIS- Declaration of Competing Interest The authors declare no conflict of interest. EDAT- 2023/10/07 00:41 MHDA- 2023/12/05 12:42 CRDT- 2023/10/06 18:07 PHST- 2022/11/29 00:00 [received] PHST- 2023/07/07 00:00 [revised] PHST- 2023/09/20 00:00 [accepted] PHST- 2023/12/05 12:42 [medline] PHST- 2023/10/07 00:41 [pubmed] PHST- 2023/10/06 18:07 [entrez] AID - S0165-0378(23)00362-5 [pii] AID - 10.1016/j.jri.2023.104156 [doi] PST - ppublish SO - J Reprod Immunol. 2023 Dec;160:104156. doi: 10.1016/j.jri.2023.104156. Epub 2023 Sep 23.