Spatial Transcriptomics Uncovers the Hybrid Molecular Identity, Ciliated Phenotype, and Immune Signature of Adenomyosis Lesions

ABSTRACT: Adenomyosis is a common gynaecological condition characterised by ectopic endometrial tissue within the myometrium, causing debilitating symptoms with limited treatment options. Despite its prevalence, the pathogenesis of adenomyosis remains poorly understood, hindering the development of targeted therapies for true disease modification rather than symptom management. The objective of this study was to elucidate the spatial transcriptomic profile of adenomyosis lesions with matched eutopic endometrial subregions, with a focus on specific cell types and tissue compartments. The study was designed to identify differentially expressed genes, functionally enriched pathways, and cell-cell communication networks within adenomyosis lesions compared to matched endometrial subregions, and to nominate potential drug targets for future therapeutic development. We show that adenomyosis lesions exhibit a distinct transcriptome intermediate between matched endometrium and myometrium, with enhanced epithelial ciliation and altered biological pathways. We reveal that lesion transcriptome is more like the endometrial basalis than the functionalis, displaying increased olfactory signalling, altered oxidative phosphorylation and ATP synthesis, and an altered immune microenvironment suggestive of chronic inflammation. In silico drug screening identified potential compounds that can reverse the adenomyosis lesion transcriptome. These findings provide insights into the molecular landscape of adenomyosis lesions and pave the way for developing novel, lesion-specific treatments that could potentially spare the eutopic endometrium and offer alternatives to hysterectomy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE303150 | GEO | 2025/12/06

REPOSITORIES: GEO