Clarifying the role of exosomal miR-137-3p in endometrial regeneration: Mechanistic gaps and future directions

This article comments on the study by Zhang et al, which proposed that exosomes derived from hypoxia-injured endometrial epithelial cells promote human umbilical cord mesenchymal stem cell migration and differentiation into endometrial epithelial cells via exosomal miR-137-3p. The authors demonstrated that miR-137-3p targets ubiquitin protein ligase E3C and activates signal transducer and activator of transcription 3 signaling, thereby driving epithelial lineage transition. While this study expands our understanding of exosome-mediated intercellular communication in endometrial repair, several key gaps remain. Notably, microRNA (miRNA) profiling was performed in human umbilical cord mesenchymal stem cells post-exosome treatment, not in the exosomes derived from hypoxia-injured endometrial epithelial cell themselves, leaving open whether miR-137-3p is directly transferred or indirectly induced. In addition, data on exosome characterization were unavailable, and the rationale for selecting miR-137-3p over other differentially expressed miRNAs was not well justified. Future studies should include direct exosomal miRNA content analysis, in vivo validation, and deeper mechanistic exploration of the ubiquitin protein ligase E3C-signal transducer and activator of transcription 3 ubiquitination axis to establish the clinical and biological relevance of this pathway.