Lipidome atlas of human myometrium reveals distinctive lipid signatures associated with adenomyosis: Combination of high-coverage lipidomics and mass spectrometry imaging

Shuo Liang, Jialin Liu, Maokun Liao, Dandan Liang, Yiyi Gong, Bo Zhang, Nan Zhao, Wei Song, Honghui Shi
Journal of pharmaceutical analysis · 2025 · vol. 15(9) , pp. 101197 · doi:10.1016/j.jpha.2025.101197 · PMID:41050115 · W4406573494
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This study profiled the human myometrium lipidome for the first time, identifying 83 altered lipid species in adenomyosis and demonstrating that five lipids could distinguish adenomyosis from controls with high accuracy.

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Abstract

Adenomyosis is a common gynecological disease characterized by the invasion of endometrial glands and stroma into the myometrium of uterus, the pathological mechanism of which remains unclear yet. Disturbed lipid metabolism extensively affects abnormal cell proliferation and invasion in various diseases. However, the lipidome signature of human myometrium, which could be crucial in the development of adenomyosis, remains unknown. In this study, we generated the first lipidome profiling of human myometrium using a high-coverage and quantitative lipidomics approach based on ultra-performance liquid chromatography (UPLC) coupled with triple quadrupole (QqQ)-mass spectrometry (MS). A total of 317 lipid species were successfully quantified in the myometrial tissues from women with ( n = 38) or without ( n = 65) adenomyosis who underwent hysterectomy at Peking Union Medical College Hospital (Bejing, China). Up to 83 lipid species showed significant alternations in content between the two groups. These lipid aberrations involved multiple metabolic pathways, and emphasized inflammation, cell migration, and immune dysregulation upon adenomyosis. Moreover, receiver operating characteristic (ROC) curve analysis found that the combination of five lipid species could accurately distinguished the myometrial samples from women with and without adenomyosis with an area under the curve (AUC) of 0.906. Desorption electrospray ionization MS imaging (MSI) further underscored the heterogeneous distributions of these lipid markers in the adenomyosis lesion and adjacent myometrial tissue. Collectively, these results extremely improved our understanding on the molecular basis of adenomyosis, and could shed light on developing potential biomarkers and new therapeutic directions for adenomyosis. • Integrated lipidome profiling of human myometrium was obtained for the first time. • Multiple lipid alternations were found in the myometrium of women with adenomyosis. • The combination of five lipids accurately distinguished adenomyosis from the controls. • Spatial heterogeneity of the five lipid markers were further revealed by MS imaging.

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adenomyosis

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