Analysis of inflammatory biomarkers IL-6, vascular endothelial growth factor and matrix metalloproteinases-9 expression in endometriosis

Maofang Hua, Wang Y, Yuan Wang, Jun Yao, Yao J, Zichun Zhu, Zhenxuan Zhu, Zhu Z, Liu X, Xiaoyun Liu, Fanfei Meng, Meng F, Yu S, Su Yu, ShuangHua Yu
SAGE open medicine · 2025 · vol. 13 , pp. 20503121251321625 · doi:10.1177/20503121251321625 · PMID:39990967 · W4407773147
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This study found increased expression of IL-6, vascular endothelial growth factor, and matrix metalloproteinases-9 in eutopic endometrial tissues of endometriosis patients, with matrix metalloproteinases-9 also elevated in peripheral blood and peritoneal fluid as disease severity increased.

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This study investigated the expression levels of inflammatory biomarkers IL-6, vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9) in patients with ovarian endometriomas categorized by American Society for Reproductive Medicine stages I-II and III-IV. The researchers compared these markers across peripheral blood, peritoneal fluid, eutopic endometrium, and ectopic endometrium using real-time polymerase chain reaction in 78 participants alongside a control group. Key findings indicated that MMP-9 expression was significantly elevated in both peripheral blood and peritoneal fluid of endometriosis patients compared to controls, while VEGF showed significant differences specifically in ectopic endometrial tissue between disease stages. This paper is centrally about endometriosis — specifically analyzing inflammatory pathways in ovarian endometriomas.

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Abstract

OBJECTIVE: Special attention has been paid to genetic mechanisms that might have a significant impact on the context of the risk of developing endometriosis, in recent years. The study aimed to analyze the expression levels of three inflammatory biomarkers Interleukin-6 (IL-6), vascular endothelial growth factor, and matrix metalloproteinases-9, in the increased incidence of endometriosis. METHODS: The material for genetic testing was tissue slices embedded in paraffin blocks from these patients with endometriosis (I-II) (n = 24), endometriosis (III-IV) (n = 24), and the control group (n = 30) in Lianyungang maternal and child health hospital from January 2020 to December 2023. The expression levels of IL-6, vascular endothelial growth factor, and matrix metalloproteinases-9 genes were determined by the real-time polymerase chain reaction technique. RESULTS: The expression levels of IL-6 and vascular endothelial growth factor gene in the peripheral blood and peritoneal fluid of these endometriosis patients were not statistically significant lower than in the control group. Besides, the significant differences were found in IL-6, vascular endothelial growth factor and matrix metalloproteinases-9 between eutopic endometrial tissues of the endometriosis group, compared to the control group; and these increased significantly with the severity of the disease. In addition, there was significant difference in the expression level of matrix metalloproteinases-9 in peripheral blood and peritoneal fluid, and the difference was statistically significant in these patients with stages III-IV, compared with these patients with stages I-II. Among them, the Revised American Society for Reproductive Medicine classification of endometriosis was used in the group of patients with endometriosis. CONCLUSION: These patients with endometriosis showed the significant differences in matrix metalloproteinases-9 expression in peripheral blood, peritoneal fluid, and eutopic and ectopic endometrial tissues as the condition worsens. The research suggested that the determination of matrix metalloproteinases-9 in peripheral blood has certain value in evaluating the condition of endometriosis, which might play an important role in the pathogenesis of endometriosis and be explored for postoperative recurrence monitoring.
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Abstract

Objective:

Methods

Results:

Conclusion

Introduction

Methods

Patients RNA isolation Real-time polymerase chain reaction IL-6forward: 5′-ACTCACCTCTTCAGAACGAATTG- 3′,reverse: 5′- CCATCTTTGGAAGGTTCAGGTTG- 3′;VEGFforward: 5′-AGGGCAGAATCATCACGAAGT- 3′,reverse: 5′-AGGGTCTCGATTGGATGGCA- 3′;MMP-9forward: 5′-GGGACGCAGACATCGTCATC- 3′,reverse: 5′-TCGTCATCGTCGAAATGGGC- 3′;β-actionforward, 5′-CCGTAAAGACCTCTATGCC- 3′,reverse, 5′-CTCAGT AACAGTCCGCCTA- 3′. Statistical analysis

Results

| Parameter | OEMs (I–II) | OEMs (III–IV) | Control | p-Value | |---|---|---|---|---| | Number of patients | 24 | 24 | 30 | | | Age, year | 31.29 ± 5.34 | 32.60 ± 5.16 | 35.10 ± 5.03 | 0.077 | | BMI, kg/m2 | 22.36 ± 2.21 | 21.59 ± 2.02 | 22.73 ± 2.99 | 0.075 | | Gravidity, n | 1.62 ± 0.91 | 1.41 ± 1.08 | 1.45 ± 0.92 | 0.569 | | Parity, n | 1.07 ± 0.78 | 1.05 ± 0.73 | 0.86 ± 0.71 | 0.312 | | Menstrual frequency, d | 28.57 ± 2.27 | 28.86 ± 1.86 | 29.50 ± 1.95 | 0.101 | | Menstrual time, d | 5.52 ± 0.89 | 5.08 ± 1.08 | 4.31 ± 1.16 | 0.137 | Analysis of inflammatory biomarker IL-6 expression in endometriosis | Parameter | OEMs (I–II) | OEMs (III–IV) | Control | p-Value | |---|---|---|---|---| | Number of patients | 24 | 24 | 30 | | | Peripheral blood | 226.73 ± 41.18 | 198.18 ± 17.75 | 234.94 ± 27.89 | 0.086 | | Peritoneal fluid | 185.05 ± 29.47 | 202.60 ± 32.62 | 143.36 ± 14.14 | 0.216 | | Eutopic endometrium | 0.5052 ± 0.02681 | 0.9154 ± 0.02183 | 1 ± 0.001962 | 0.042 | | Ectopic endometrium | 9.618 ± 0.1395 | 11.782 ± 0.2314 | — | 0.153 | Analysis of inflammatory biomarker VEGF expression in endometriosis | Parameter | OEMs (I–II) | OEMs (III–IV) | Control | p-Value | |---|---|---|---|---| | Number of patients | 24 | 24 | 30 | | | Peripheral blood | 257.6 ± 24.6 | 326.6 ± 7.8 | 158.9 ± 16.1 | 0.641 | | Peritoneal fluid | 89.9 ± 6.9 | 122.7 ± 9.1 | 75.2 ± 6.2 | 0.332 | | Eutopic endometrium | 0.5535 ± 0.003389 | 0.5136 ± 0.003289 | 1 ± 0.003314 | 0.042 | | Ectopic endometrium | 3.228 ± 0.0355 | 6.828 ± 0.0435 | — | 0.041 | Analysis of inflammatory biomarker MMP-9 expression in endometriosis | Parameter | OEMs (I–II) | OEMs (III–IV) | Control | p-Value | |---|---|---|---|---| | Number of patients | 24 | 24 | 30 | | | Peripheral blood | 1090.22 ± 108 | 2430 ± 219.2 | 258.25 ± 49.3 | <0.0001 | | Peritoneal fluid | 1431.3 ± 96.6 | 2775.5 ± 112.2 | 589.8 ± 37.6 | <0.0001 | | Eutopic endometrium | 1.669 ± 0.05226 | 1.587 ± 0.05226 | 1.000 ± 0.03181 | 0.0002 | | Ectopic endometrium | 2.664 ± 0.01993 | 2.984 ± 0.01993 | - | 0.315 |

Discussion

Conclusions Acknowledgments Ethics approval Informed consent Declaration of conflicting interests Funding ORCID iD Footnote Data availability statement

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Data availability statement Authors Author contributions Metrics and citations Metrics Publication usage* Total views and downloads: 622 *Publication usage tracking started in December 2016 Altmetric See the impact this article is making through the number of times it’s been read, and the Altmetric Score. Learn more about the Altmetric Scores Publications citing this one Receive email alerts when this publication is cited Web of Science: 2 view articles Opens in new tab Crossref: 4 - Stem cell therapy-based approaches in experimental endometriosis: a systematic review - Altered miR‐410‐3p and Target Genes (PCDH8, VEGFA, NUMB) Expression in Ovarian Endometriosis: A Case‐Control Study - Enhancement of skin defense against UVB damage by fermentation of Leonurus japonicus with Saccharomyces cerevisiae - Objectification of Pain in Patients with Endometriosis. (Literature review and own data) Figures and tables Figures & Media Tables View Options View options PDF/EPUB View PDF/EPUBAccess options If you have access to journal content via a personal subscription, university, library, employer or society, select from the options below: loading institutional access options Alternatively, view purchase options below: Access journal content via a DeepDyve subscription or find out more about this option.

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