Ono Yosuke, Tanaka Kota, Sato Erina, Ito Masami, Zhang Di, Honda Masako, Ogawa Tatsuyuki, Tagaya Hikaru, Fukuda Tomohiko, Shinozaki Youichi, Kato Kazuyoshi, Koizumi Schuichi, Yoshino Osamu
Department of Obstetrics and Gynecology, University of Yamanashi, Chuo, Japan.
Department of Obstetrics and Gynecology, Kitasato University School of Medicine, Sagamihara, Japan.
Sci Rep. 2025 Jul 31;15(1):28015. doi: 10.1038/s41598-025-13855-x.
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.
子宫内膜异位症的纤维化机制尚未阐明。我们研究了嗜酸性粒细胞在子宫内膜异位症纤维化中的作用。对子宫内膜异位症基质细胞（ESCs）和子宫内膜上皮细胞（EECs）进行了体外实验。在子宫内膜异位症病变中，苏木精-伊红（HE）染色显著观察到嗜酸性粒细胞。对嗜酸性粒细胞颗粒蛋白主要碱性蛋白（MBP）进行免疫组织化学染色，结果显示MBP阳性嗜酸性粒细胞主要存在于上皮细胞层下方的子宫内膜基质区域。在18例卵巢子宫内膜异位囊肿（EMoma）病例中，有17例发现嗜酸性粒细胞簇，相比之下，16例非子宫内膜异位性卵巢囊肿/肿瘤（非EMoma）中有3例出现（P < 0.0005）。HE染色显示纤维化区域有嗜酸性粒细胞，每100×100μm区域内嗜酸性粒细胞≥3个的视野中，核仁阳性成纤维细胞计数更高（P < 0.05）。连续进行的Masson三色染色显示，MBP阳性嗜酸性粒细胞周围有蓝色染色的细胞外基质，表明存在纤维化。嗜酸性粒细胞刺激因子GM-CSF水平在EMoma内容物中（93.6 ± 16.9 pg/ml）高于非EMoma（3.6 ± 2.1 pg/ml，P < 0.05）。嗜酸性粒细胞与ESCs或EECs共培养上调了PAI-1 mRNA和蛋白表达。免疫组织化学证实PAI-1在嗜酸性粒细胞丰富的病变中表达。这些发现表明，嗜酸性粒细胞通过诱导PAI-1促进子宫内膜异位症的纤维化，提供了新的治疗靶点。
