FOXL2 Knockdown Inhibits the Progression of Endometriosis

Bing Zhang, Li SJ, Shang-Jin Li, Yuan H, Hua Yuan, Shan-Shan Cong, Cong SS, Shao-Jie Zhao, Zhao SJ, Xiao-Jun Yang, Xiao‐Jun Yang
American journal of reproductive immunology (New York, N.Y. : 1989) · 2025 · vol. 93(1) , pp. e70043 · doi:10.1111/aji.70043 · PMID:39776079
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⚙ AI-generated summary by claude@2026-08, 2026-08-03 ⓘ

FOXL2 knockdown in rats and isolated ectopic endometrial stromal cells reduced endometriosis progression, suppressed cell proliferation, migration, and invasion, and increased apoptosis by impacting epithelial-mesenchymal transition and ER signaling.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-23 · read from full text ⓘ

This paper studied whether Forkhead box L2 (FOXL2) regulates the occurrence and progression of endometriosis using an EM model in rats and isolated ectopic endometrial stromal cells (EC-ESCs). FOXL2 knockdown was assessed by HE staining for ectopic pathology, RT-qPCR and immunohistochemistry for FOXL2, estrogen receptor (ER-α/ER-ß), Cyp19a, and epithelial-to-mesenchymal transition–related markers, and functional assays (EDU, Transwell, flow cytometry) with cleaved-Caspase3 measurements. FOXL2 was higher in ectopic endometrial tissue than in normal tissue, and knockdown improved rat pathological morphology while decreasing ER-α, ER-ß, and Cyp19a expression; in EC-ESCs, FOXL2 suppression reduced proliferation, migration, and invasion and increased apoptosis with higher cleaved-Caspase3 and cleaved-Caspase3/Caspase3 ratio. Limitations include reliance on rat and cell models rather than direct human evidence for mechanism. This paper is centrally about endometriosis — it tests FOXL2 knockdown as an inhibitor of EM progression via EMT and stromal cell invasion/migration changes.

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Abstract

PROBLEM: Endometriosis (EM) is known as a common estrogen-dependent chronic inflammatory disease. Elevated levels of Forkhead box L2 (FOXL2) have been observed in uterine diseases, including EM. However, the molecular mechanism of FOXL2 in EM needs to be further illustrated. This study aimed to investigate the regulatory role of FOXL2 in EM rats and isolated ectopic endometrial stromal cells (EC-ESCs). METHOD OF STUDY: FOXL2 knockdown were designed to evaluate the effects of FOXL2 in EM model rats and EC-ESCs. Hematoxylin-eosin (HE) staining was used to evaluate the pathological morphology of ectopic endometrium. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) analysis and immunohistochemistry (IHC) were applied to detect the expression of FOXL2, EM-related genes, and epithelial to mesenchymal transition-related proteins. The proliferation, migration, invasion, and apoptosis of EC-ESCs were determined by 5-ethynyl-2'-deoxyuridine (EDU) assay, Transwell assay, and flow cytometry. RESULTS: The FOXL2 level was remarkably higher in the ectopic endometrial tissue than that in the normal endometrial tissue. Knockdown of FOXL2 notably improved the pathological morphology of EM in rats, and decreased expression levels of ER-α, ER-ß, and Cyp19a. Additionally, down-regulation of FOXL2 suppressed cells proliferation, migration and invasion, and stimulated more apoptotic cells in EC-ESCs. Besides, FOXL2-small interfering RNA (FOXL2-siRNA) treatment resulted in enhanced cleaved-Caspase3 protein expression and cleaved-Caspase3/Caspase3 ratio in EC-ESCs. CONCLUSION: FOXL2 participates in the occurrence and development of EM through promoting epithelial-mesenchymal transition procession and enhancing the migration and invasion of EC-ESCs, suggesting that FOXL2 may be a new therapeutic target for the EM therapy.
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Abstract

Problem Endometriosis (EM) is known as a common estrogen-dependent chronic inflammatory disease. Elevated levels of Forkhead box L2 (FOXL2) have been observed in uterine diseases, including EM. However, the molecular mechanism of FOXL2 in EM needs to be further illustrated. This study aimed to investigate the regulatory role of FOXL2 in EM rats and isolated ectopic endometrial stromal cells (EC-ESCs).

Method

of Study FOXL2 knockdown were designed to evaluate the effects of FOXL2 in EM model rats and EC-ESCs. Hematoxylin-eosin (HE) staining was used to evaluate the pathological morphology of ectopic endometrium. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) analysis and immunohistochemistry (IHC) were applied to detect the expression of FOXL2, EM-related genes, and epithelial to mesenchymal transition-related proteins. The proliferation, migration, invasion, and apoptosis of EC-ESCs were determined by 5-ethynyl-2′-deoxyuridine (EDU) assay, Transwell assay, and flow cytometry.

Results

The FOXL2 level was remarkably higher in the ectopic endometrial tissue than that in the normal endometrial tissue. Knockdown of FOXL2 notably improved the pathological morphology of EM in rats, and decreased expression levels of ER-α, ER-ß, and Cyp19a. Additionally, down-regulation of FOXL2 suppressed cells proliferation, migration and invasion, and stimulated more apoptotic cells in EC-ESCs. Besides, FOXL2-small interfering RNA (FOXL2-siRNA) treatment resulted in enhanced cleaved-Caspase3 protein expression and cleaved-Caspase3/Caspase3 ratio in EC-ESCs.

Conclusion

FOXL2 participates in the occurrence and development of EM through promoting epithelial-mesenchymal transition procession and enhancing the migration and invasion of EC-ESCs, suggesting that FOXL2 may be a new therapeutic target for the EM therapy. Conflicts of Interest The authors declare no conflicts of interest. Data Availability Statement The data used to support the findings of this study are available from the corresponding author upon request.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

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SciLite annotations

chemicals 3
estrogen haematoxylin 2'-deoxyuridine
organisms 2
rattus sp. rattus sp.

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