Spatial and single-cell transcriptomics landscape of adenomyosis

Area of Science:

• Gynecological disorders
• Reproductive medicine
• Cellular and molecular mechanisms

Background:

• Adenomyosis is a common gynecological disorder with poorly understood causes.
• Gonadotropin-releasing hormone agonists (GnRHa) are used to treat adenomyosis, but their cellular effects are unclear.

Purpose of the Study:

• To profile adenomyosis using single-cell and spatial transcriptomics.
• To evaluate the effects of GnRHa treatment on cellular populations in adenomyosis.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (Geo-seq) were used.
• 15 participants (11 adenomyosis, 4 controls) were profiled.
• Immunofluorescence and immunohistochemistry validated findings.

Main Results:

• Ectopic endometrial glands in adenomyosis showed enrichment of ciliated epithelial cells.
• Immune-inflammatory signatures (CD4+ T cells, LYVE1+ macrophages) were prominent in untreated adenomyosis.
• GnRHa treatment partially mitigated inflammation and angiogenesis; mast cells were concentrated in the junctional zone.

Conclusions:

• Findings support the invagination theory, implicating ciliated cells and immune-angiogenic crosstalk.
• GnRHa normalizes immune cell composition and epithelial-stromal interactions.
• Novel mechanistic insights into GnRHa's therapeutic action were provided.