Single-cell profiling of endometriosis-associated macrophages and ferroptosis-modulating effects of lemon-derived extracellular vesicles

Endometriosis is associated with altered immune responses and fibrotic remodeling. We integrated single-cell transcriptomic analysis of eutopic endometrium from women with endometriosis and controls with experimental evaluation of lemon-derived extracellular vesicles (LDEVs). Transcriptomic analysis identified an oxidative stress-associated macrophage state and predicted altered interactions with stromal and epithelial cells. Integrative analysis highlighted ACSL1 as a candidate ferroptosis-related molecular node. In RAW264.7 macrophages, LDEVs increased GPX4 mRNA and decreased TFRC and ACSL1 expression. Under RSL3 challenge, LDEV pretreatment attenuated ACSL4 upregulation. In an experimental model of endometriosis, LDEV treatment reduced ectopic lesion burden and collagen deposition, accompanied by increased GPX4 and decreased ACSL1 and ACSL4 staining. These findings support further investigation of LDEVs as a potential non-hormonal therapeutic strategy for endometriosis.