Spatial Transcriptomics Atlas Maps Lesion-Specific Signatures in Adenomyosis, Identifying Druggable Inflammatory and Metabolic Targets

The study applied spatial transcriptomics to matched lesional and healthy myometrial samples from the same patients, preserving spatial architecture that bulk RNA-seq cannot. This approach identified a stable basal-layer molecular program within lesions, ongoing NF-κB-driven inflammation, and dysregulated oxidative phosphorylation that were absent in neighboring endometrium. These features explain both symptom persistence and the failure of non-specific hormonal suppression.

Existing therapies remain limited to levonorgestrel-releasing systems or hysterectomy because no lesion-selective agents exist. The atlas nominates several already-approved compounds whose targets align with the observed signatures, offering a rapid repurposing route that could avoid fertility loss. This is particularly relevant given adenomyosis prevalence of up to 20 % in reproductive-age women and its frequent misdiagnosis as endometriosis.

The work underscores a broader pattern: underfunded benign gynecologic diseases yield high translational returns once spatially resolved molecular data replace descriptive histology. Next steps require validation in larger, multi-ethnic cohorts and functional testing of nominated compounds in patient-derived organoids before any clinical trial design.