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CSF1‐associated decrease in endometrial macrophages may contribute to Asherman's syndrome
Author(s) -
Liu Dan,
Wang Jiali,
Zhao Guangfeng,
Jiang Peipei,
Song Minmin,
Ding Hailin,
Wang Zhiyin,
Lv Haining,
Hu Yali
Publication year - 2020
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.13191
Subject(s) - fibrosis , endometrium , stromal cell , pathology , masson's trichrome stain , immunostaining , inflammation , immunohistochemistry , biology , andrology , medicine , immunology , endocrinology
Problem Asherman's syndrome (AS) is characterized by endometrial fibrosis leading to intrauterine adhesions and symptoms like hypomenorrhea, infertility, and recurrent pregnancy loss. Macrophages are key regulators of inflammation, tissue repair, regeneration, and fibrosis. However, the role of macrophages in AS remains unclear. Method of study Endometrial biopsies of AS patients and controls were collected during the late proliferating phase of menstrual cycle. Fibrosis and proliferation markers were detected by Masson's trichrome staining and immunohistochemistry. Macrophages were examined by immunostaining and flow cytometry. The expression levels of CCL2, CSF1, CSF1R, and GM‐CSF were detected by quantitative real‐time polymerase chain reaction (q‐PCR) and immunohistochemistry. A well‐differentiated endometrial cell line Ishikawa (IK) was used for in vitro studies. Macrophages differentiating from THP‐1 monocytic cells were polarized by IL‐4/IL‐13. Their culture supernatants (M(IL‐4/13)‐S) were applied to H 2 O 2 or bleomycin‐damaged IK cells. Results In AS patients, endometrial stroma was replaced by fibrous tissue and cell proliferation was reduced. Macrophages in endometrial tissue were mainly alternative activated macrophages and their number was significantly decreased in AS patients. The CSF1 expression level was reduced in AS patients. M(IL‐4/13)‐S promoted the growth and migration of IK cells and inhibited H 2 O 2 ‐induced apoptosis. M(IL‐4/13)‐S protected IK cells from bleomycin‐induced fibrosis. Conclusion Macrophages are critical cells involved in the process of endometrial repair and fibrosis. The decreased amount of endometrial macrophages may be attributed to the reduced expression level of CSF1. Manipulation of macrophage activation/function may provide a novel therapeutic target for AS.