Dysfunctional intercellular communication and metabolic signaling pathways in thin endometrium

Area of Science:

• Reproductive Biology
• Genomics
• Cellular and Molecular Medicine

Background:

• Endometrial thickness is crucial for successful embryo implantation.
• Thin endometrium is associated with reduced implantation and pregnancy rates.
• Understanding the cellular and molecular mechanisms of thin endometrium remains a clinical challenge.

Purpose of the Study:

• To investigate the cellular and molecular mechanisms underlying thin endometrium.
• To identify disease-specific cell types and signaling pathways in thin endometrium.
• To explore differential intercellular communication and metabolic pathways in thin endometrium.

Main Methods:

• Integrated analysis of four single-cell RNA sequencing (scRNA-seq) and one bulk sequencing (bulk-seq) datasets.
• Analysis of cell proportions and differentially expressed genes (DEGs) in endometrial cells.
• Inference of cell-cell communication using CellChat and pathway analysis via GSEA and GSVA.

Main Results:

• Eight distinct endometrial cell types were identified, with significant differences in stromal cell proportions.
• DEGs revealed cell-specific enriched pathways and aberrant cell-cell signaling, particularly in immune and epithelial cells.
• Dysfunctional metabolic pathways, including down-regulation of carbohydrate and nucleotide metabolism, were observed, indicating an energy metabolism shift.

Conclusions:

• This study elucidates dysfunctional signaling and metabolic pathways in thin endometrium.
• Findings provide novel insights into the mechanisms contributing to atrophic endometrium.
• The results may guide the development of targeted therapeutic strategies for thin endometrium.