SEMA3F对子宫内膜异位症患者子宫内膜间质细胞增殖、迁移和铁死亡的影响

Effect of SEMA3F on Proliferation, Migration, and Ferroptosis of Endometrial Stromal Cells in Patients with Endometriosis.

作者信息

Zheng Yi, Zhou Yu, Wang Caizhi, Liu Shuyu

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China.

出版信息

Gynecol Obstet Invest. 2025 May 2:1. doi: 10.1159/000545947.

DOI:10.1159/000545947

PMID:40319865

Abstract

INTRODUCTION

The objective of this study was to examine the impact of semaphorin 3F (SEMA3F) on the proliferation, migration and ferroptosis of endometrial stromal cells in patients with endometriosis (EMS).

METHODS

This study collected ectopic endometriotic tissues from 30 patients with EMS (EMS group) and eutopic endometrial tissues from 30 patients in the control group who underwent hysterectomy due to uterine fibroids. The ectopic endometriotic tissues were sourced from the cystic walls of ovarian endometriomas in women with EMS. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting were adopted to evaluate SEMA3F expression of endometrial tissues. Endometrial stromal cells (ESCs) were isolated from ectopic endometriotic tissues and divided into the oe-NC group, oe-SEMA3F group, and a blank group (non-transfected). SEMA3F expression in cells was quantified by RT-qPCR and Western blotting. Cell proliferation was quantified with the Cell Counting Kit-8 (CCK-8) assay, and migration and invasion were analyzed via the Transwell method. Ferroptosis markers (Fe2+, malondialdehyde [MDA], glutathione [GSH]) and ferroptosis-related proteins (ACSL4, PTGS2) were evaluated with Western blotting, and inflammatory factors (IL-6, TNF-α) were measured using enzyme-linked immunosorbent assay.

RESULTS

Levels of both mRNA and protein in SEMA3F were lower in the ectopic endometriotic endometrial tissue of EMS patients compared to controls. Overexpression of SEMA3F in ESCs from patients with EMS reduced cellular activity, migration, and invasion. Additionally, Fe2+, MDA, and other ferroptosis markers were significantly reduced, while GSH levels increased. Ferroptosis-related protein expression (ACSL4, PTGS2) was suppressed, and inflammatory factor levels (IL-6, TNF-α) decreased.

CONCLUSION

SEMA3F may regulate the development of EMS by affecting the proliferation, invasion, migration, as well as ferroptosis of ESCs from patients with EMS.

摘要

引言

本研究旨在探讨信号素3F（SEMA3F）对子宫内膜异位症（EMS）患者子宫内膜间质细胞增殖、迁移和铁死亡的影响。

方法

本研究收集了30例EMS患者的异位子宫内膜组织（EMS组）和30例因子宫肌瘤行子宫切除术的对照组患者的在位子宫内膜组织。异位子宫内膜组织取自EMS女性患者卵巢子宫内膜异位囊肿壁。采用逆转录-定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法评估子宫内膜组织中SEMA3F的表达。从异位子宫内膜组织中分离出子宫内膜间质细胞（ESCs），分为空载对照组（oe-NC组）、SEMA3F过表达组（oe-SEMA3F组）和空白组（未转染）。通过RT-qPCR和蛋白质免疫印迹法对细胞中SEMA3F的表达进行定量。用细胞计数试剂盒-8（CCK-8）法对细胞增殖进行定量，通过Transwell法分析细胞迁移和侵袭能力。采用蛋白质免疫印迹法评估铁死亡标志物（Fe2+、丙二醛[MDA]、谷胱甘肽[GSH]）和铁死亡相关蛋白（ACSL4、PTGS2），使用酶联免疫吸附测定法检测炎症因子（IL-6、TNF-α）。

结果

与对照组相比，EMS患者异位子宫内膜组织中SEMA3F的mRNA和蛋白水平均较低。EMS患者ESCs中SEMA3F的过表达降低了细胞活性、迁移和侵袭能力。此外，Fe2+、MDA和其他铁死亡标志物显著降低，而GSH水平升高。铁死亡相关蛋白表达（ACSL4、PTGS2）受到抑制，炎症因子水平（IL-6、TNF-α）降低。