Unraveling the VEGF-ETS1 axis: a transcriptomic and single-cell analysis of angiogenesis in endometriosis

Liu X, Xiaoxuan Liu, An R, Ran An, Ping Zhang, Zhang P, Yang Q, Qi Yang, Shuang Wang, Wang S, Jiao X, Xue Jiao, Le Xu, Xu L, Qianhui Ren, Ren Q, Guoyun Wang
Journal of assisted reproduction and genetics · 2026 · vol. 43(3) , pp. 979–995 · doi:10.1007/s10815-025-03781-2 · PMID:41543773 · PMC12982733
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⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-24 ⓘ

This study identifies the VEGF-ETS1 axis, driven by ETS1 upregulation in endothelial cells, as a central mechanism promoting pathological angiogenesis and vascular remodeling in endometriosis lesions.

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Abstract

PURPOSE: Endometriosis (EM) is a chronic inflammatory gynecological disorder characterized by ectopic endometrial-like lesions, where aberrant angiogenesis is a hallmark driving lesion establishment and progression. However, the transcriptional mechanisms underlying pathological vascular remodeling in EM remain unclear. METHODS: In this study, we identified E26 transformation-specific 1 (ETS1) as a key transcriptional regulator in EM pathogenesis through integrative analysis of bulk and single-cell transcriptomic datasets. RESULTS: Across three independent transcriptome datasets and two validation cohorts, ETS1 expression was consistently elevated in endometriosis lesions, particularly in ovarian endometrioma. Single-cell RNA sequencing further revealed that ETS1 was predominantly expressed in endothelial cells and dynamically upregulated along the endothelial differentiation trajectory. Functional enrichment and pseudotime analyses indicated that ETS1 + endothelial cells exhibited enhanced angiogenic activity and vascular remodeling potential. Mechanistically, ETS1 amplified VEGF signaling by upregulating VEGFR1 and VEGFR2, while macrophage-derived VEGFA acted as the principal upstream activator within the lesion microenvironment. CONCLUSIONS: Collectively, our findings delineate the VEGF-ETS1 axis as a central driver of pathological angiogenesis in endometriosis, positioning ETS1 as both a mechanistic hallmark and a promising therapeutic target for endometriosis.

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Condition tags

endometriosisendometrioma

MeSH descriptors

Angiogenesis Angiogenesis Angiogenesis Angiogenesis Angiogenesis Angiogenesis Angiogenesis Angiogenesis Angiogenesis Angiogenesis Angiogenesis Angiogenesis Angiogenesis Angiogenesis Angiogenesis Angiogenesis Angiogenesis Angiogenesis Angiogenesis Angiogenesis

Funding

funders
[{'doi': None, 'name': 'The National Key R&D Program of China', 'awards': ['2022YFC2704000']}, {'doi': None, 'name': 'the Special foundation for Taishan Scholars', 'awards': ['No. tstp20230657']}, {'doi': None, 'name': 'the Major Basic Research of Natural Science Foundation of Shandong', 'awards': ['ZR2021ZD34']}, {'doi': '10.13039/501100001809', 'name': 'the National Natural Science Foundation of China', 'awards': ['grant numbers 82371653']}, {'doi': '10.13039/501100001809', 'name': 'the National Natural Science Foundation of China', 'awards': ['82071621']}, {'doi': None, 'name': 'General Project of Shandong Natural Science Foundation', 'awards': ['ZR2023MH177']}]

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References (38)

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