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

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.