ArticleBMC medicine2026
Ionomics powered single-cell mapping reveals targetable iron dysregulation in endometriosis associated macrophages.
Article in BMC medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundEndometriosis affects approximately 10% of women of reproductive age worldwide. Although elemental components of refluxed menstrual blood have been implicated in disease progression, comprehensive ionomic profiling of the endometriotic microenvironment remains limited. Characterizing the localized elemental landscape may generate new hypotheses regarding disease mechanisms.
methodsWe employed inductively coupled plasma mass spectrometry (ICP-MS) to profile 63 elements in endometriotic cyst fluid. Single-cell RNA sequencing (scRNA-seq) was performed to explore cellular subpopulations potentially associated with elemental dysregulation. Senescent red blood cells (sRBCs) were used to model retrograde menstruation in endometriosis. The effects of iron chelation with deferoxamine (DFO) and ferroptosis inhibition with ferrostatin-1 (Fer-1) were evaluated.
resultsICP-MS identified iron as the most significantly elevated element in patients with endometriosis, supported by flow cytometry and Prussian blue staining. ScRNA-seq revealed a macrophage subcluster enriched in endometriotic lesions, co-expressing M2-associated markers and ferroptosis-related genes. Mechanistically, sRBC phagocytosis activated HIF-1α and HO-1 expression in macrophages, accompanied by intracellular iron accumulation, sublethal ferroptotic stress characterized by elevated lipid peroxidation and reactive oxygen species, M2-like polarization, and impaired phagocytic capacity. These iron-laden macrophages suppressed CD8
conclusionsThis exploratory study suggests that sRBC-derived iron overload may be associated with a shift of macrophages toward an immunosuppressive phenotype, potentially linked to the HIF-1α/HO-1/GPX4 pathway. These changes may contribute to local immune dysfunction in endometriosis. These findings highlight macrophage iron metabolism as a potential therapeutic target that warrants validation in larger and independent cohorts.
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