Activated eosinophil plays a role in promoting fibrosis in endometriotic lesion
Abstract The fibrosis mechanism in endometriosis is not elucidated. We investigated the role of eosinophil in fibrosis of endometriosis. The endometriotic stromal cells (ESCs) and endometrial epithelial cells (EECs) were subjected to in vitro experiments. Within endometriotic lesions, eosinophils we...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-13855-x |
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| author | Yosuke Ono Kota Tanaka Erina Sato Masami Ito Di Zhang Masako Honda Tatsuyuki Ogawa Hikaru Tagaya Tomohiko Fukuda Youichi Shinozaki Kazuyoshi Kato Schuichi Koizumi Osamu Yoshino |
| author_facet | Yosuke Ono Kota Tanaka Erina Sato Masami Ito Di Zhang Masako Honda Tatsuyuki Ogawa Hikaru Tagaya Tomohiko Fukuda Youichi Shinozaki Kazuyoshi Kato Schuichi Koizumi Osamu Yoshino |
| author_sort | Yosuke Ono |
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| description | Abstract The fibrosis mechanism in endometriosis is not elucidated. We investigated the role of eosinophil in fibrosis of endometriosis. The endometriotic stromal cells (ESCs) and endometrial epithelial cells (EECs) were subjected to in vitro experiments. Within endometriotic lesions, eosinophils were prominently observed by Hematoxylin-Eosin (HE) staining. Immunohistochemical staining for Major Basic Protein (MBP), a granule protein of eosinophils, revealed that MBP-positive eosinophils were predominantly found in the endometrial stromal region beneath the epithelial cell layer. Eosinophil clusters were found in 17 of 18 ovarian endometrioma (EMoma) cases, compared to 3 of 16 in non-endometriotic ovarian cyst/tumor (non-EMoma) (P < 0.0005). HE staining revealed eosinophils in fibrotic areas, and fields with ≥ 3 eosinophils per 100 × 100 μm area showed higher counts of nucleolus-positive fibroblasts (P < 0.05). Serial Masson Trichrome staining revealed blue-stained extracellular matrix around MBP-positive eosinophils, indicating fibrosis. GM-CSF levels, a stimulator of eosinophils, were higher in EMoma contents (93.6 ± 16.9 pg/ml) compared to non-EMoma (3.6 ± 2.1 pg/ml, P < 0.05). Coculture of eosinophils with ESCs or EECs upregulated PAI-1 mRNA and protein expression. Immunohistochemistry confirmed PAI-1 expression in eosinophil-rich lesions. These findings suggest that eosinophils promote fibrosis in endometriosis through PAI-1 induction, offering new therapeutic targets. |
| format | Article |
| id | doaj-art-91d2a1fbcfa645f48c3e75dbfe2e7b6b |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-91d2a1fbcfa645f48c3e75dbfe2e7b6b2025-08-20T04:02:46ZengNature PortfolioScientific Reports2045-23222025-07-011511910.1038/s41598-025-13855-xActivated eosinophil plays a role in promoting fibrosis in endometriotic lesionYosuke Ono0Kota Tanaka1Erina Sato2Masami Ito3Di Zhang4Masako Honda5Tatsuyuki Ogawa6Hikaru Tagaya7Tomohiko Fukuda8Youichi Shinozaki9Kazuyoshi Kato10Schuichi Koizumi11Osamu Yoshino12Department of Obstetrics and Gynecology, University of YamanashiDepartment of Obstetrics and Gynecology, University of YamanashiDepartment of Obstetrics and Gynecology, Kitasato University School of MedicineDepartment of Obstetrics and Gynecology, University of ToyamaDepartment of Obstetrics and Gynecology, University of YamanashiDepartment of Obstetrics and Gynecology, Kitasato University School of MedicineDepartment of Obstetrics and Gynecology, University of YamanashiDepartment of Obstetrics and Gynecology, University of YamanashiDepartment of Obstetrics and Gynecology, University of YamanashiTokyo Metropolitan Institute of Medical ScienceDepartment of Obstetrics and Gynecology, Kitasato University School of MedicineDepartment of Neuropharmacology Interdisciplinary Graduate School of Medicine, University of YamanashiDepartment of Obstetrics and Gynecology, University of YamanashiAbstract The fibrosis mechanism in endometriosis is not elucidated. We investigated the role of eosinophil in fibrosis of endometriosis. The endometriotic stromal cells (ESCs) and endometrial epithelial cells (EECs) were subjected to in vitro experiments. Within endometriotic lesions, eosinophils were prominently observed by Hematoxylin-Eosin (HE) staining. Immunohistochemical staining for Major Basic Protein (MBP), a granule protein of eosinophils, revealed that MBP-positive eosinophils were predominantly found in the endometrial stromal region beneath the epithelial cell layer. Eosinophil clusters were found in 17 of 18 ovarian endometrioma (EMoma) cases, compared to 3 of 16 in non-endometriotic ovarian cyst/tumor (non-EMoma) (P < 0.0005). HE staining revealed eosinophils in fibrotic areas, and fields with ≥ 3 eosinophils per 100 × 100 μm area showed higher counts of nucleolus-positive fibroblasts (P < 0.05). Serial Masson Trichrome staining revealed blue-stained extracellular matrix around MBP-positive eosinophils, indicating fibrosis. GM-CSF levels, a stimulator of eosinophils, were higher in EMoma contents (93.6 ± 16.9 pg/ml) compared to non-EMoma (3.6 ± 2.1 pg/ml, P < 0.05). Coculture of eosinophils with ESCs or EECs upregulated PAI-1 mRNA and protein expression. Immunohistochemistry confirmed PAI-1 expression in eosinophil-rich lesions. These findings suggest that eosinophils promote fibrosis in endometriosis through PAI-1 induction, offering new therapeutic targets.https://doi.org/10.1038/s41598-025-13855-xEosinophilFibrosisGranulocyte-Macrophage Colony-Stimulating factor (GM-CSF)Major Basic Protein (MBP)Plasminogen activator inhibitor-1 (PAI-1) |
| spellingShingle | Yosuke Ono Kota Tanaka Erina Sato Masami Ito Di Zhang Masako Honda Tatsuyuki Ogawa Hikaru Tagaya Tomohiko Fukuda Youichi Shinozaki Kazuyoshi Kato Schuichi Koizumi Osamu Yoshino Activated eosinophil plays a role in promoting fibrosis in endometriotic lesion Scientific Reports Eosinophil Fibrosis Granulocyte-Macrophage Colony-Stimulating factor (GM-CSF) Major Basic Protein (MBP) Plasminogen activator inhibitor-1 (PAI-1) |
| title | Activated eosinophil plays a role in promoting fibrosis in endometriotic lesion |
| title_full | Activated eosinophil plays a role in promoting fibrosis in endometriotic lesion |
| title_fullStr | Activated eosinophil plays a role in promoting fibrosis in endometriotic lesion |
| title_full_unstemmed | Activated eosinophil plays a role in promoting fibrosis in endometriotic lesion |
| title_short | Activated eosinophil plays a role in promoting fibrosis in endometriotic lesion |
| title_sort | activated eosinophil plays a role in promoting fibrosis in endometriotic lesion |
| topic | Eosinophil Fibrosis Granulocyte-Macrophage Colony-Stimulating factor (GM-CSF) Major Basic Protein (MBP) Plasminogen activator inhibitor-1 (PAI-1) |
| url | https://doi.org/10.1038/s41598-025-13855-x |
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