Varied cellular abnormalities in thin vs. normal endometrium in recurrent implantation failure by single-cell...

Area of Science:

• Reproductive Biology
• Genomics
• Cellular Biology

Background:

• Recurrent implantation failure (RIF) is often linked to reduced endometrial thickness and receptivity.
• Understanding the molecular and cellular differences between these RIF subtypes is crucial for improving fertility treatments.

Purpose of the Study:

• To elucidate the molecular signatures, cellular interactions, and structural changes in RIF patients with thin endometrium (TE-RIF) versus normal endometrium (NE-RIF).
• To compare these RIF groups with fertile controls using single-cell transcriptomics.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) for transcriptomic profiling.
• Electron microscopy and histology (H&E staining) for ultrastructural and morphological analysis.
• Immunohistochemistry for protein marker localization.

Main Results:

• TE-RIF patients showed dysregulation in TNF and MAPK signaling pathways, affecting stromal cell growth and receptivity.
• NE-RIF patients exhibited disturbances in energy metabolism impacting endometrial receptivity.
• Aberrant epithelial-stromal cell communication was identified in TE-RIF, further compromising receptivity.

Conclusions:

• RIF presents heterogeneous molecular and cellular profiles depending on endometrial thickness.
• These findings offer insights for developing targeted therapies to enhance endometrial receptivity and improve assisted reproductive technology (ART) outcomes.