Eutopic macrophages facilitate endometriosis progression via ferroptosis-mediated release of S100A9

Chunying Ye, Pei Ma, Panmei Ma, Nana Li, Ruyi Zhang, Jie Wang, Zihan Zhou, Jing Wu, Dan Liu, Jiawen Sun, Jun Sun, Weichen Pan, Guangfeng Zhao, Qiao Weng
Molecular human reproduction · 2025 · vol. 31(2) · doi:10.1093/molehr/gaaf027 · PMID:40493892 · W4411168776
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

Eutopic macrophages in endometriosis patients exhibit increased ferroptosis and S100A9 expression, which promotes angiogenesis and lesion growth, suggesting S100A9 as a therapeutic target.

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Abstract

Endometriosis is a chronic inflammatory disorder in which immune cells, specifically macrophages, play a pivotal yet incompletely understood role. Aberrations within the eutopic endometrium are implicated in the initiation and progression of endometriosis. In this study, we reported a notable increase in the proportion of a distinct S100A9+ macrophage subpopulation undergoing ferroptosis in the eutopic endometrium of endometriosis patients compared with normal endometrium, as evidenced by single-cell RNA sequencing and experimental validation. Furthermore, we confirmed that Ammonium iron (III) citrate-treated macrophages upregulate S100A9 through the NF-κB pathway in vitro. Subsequent cell function experiments and endometriosis mouse models revealed that S100A9 promotes the development of endometriosis by facilitating angiogenesis. Notably, the S100A9 inhibitor Tasquinimod effectively reduced angiogenesis and thereby reduced ectopic lesions in mice. These results indicated that S100A9+ macrophages represent a potential therapeutic target for endometriosis.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Calgranulin B Calgranulin B Calgranulin B Calgranulin B Calgranulin B Calgranulin B Calgranulin B Calgranulin B Calgranulin B Calgranulin B Calgranulin B Calgranulin B Calgranulin B Calgranulin B Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (61)

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