Exosomal miR‐203a‐3p Enhances Endometrial Receptivity by Upregulating E‐Cadherin Expression Through the Direct Targeting of SNAI1 in Endometrial Epithelial Cells

Purpose Endometrial receptivity is a critical determinant of successful embryo implantation and is intricately linked to the pathophysiology of infertility. This study aimed to elucidate the role of exosomal miR‐203a‐3p in regulating endometrial receptivity, thereby providing insights into potential therapeutic strategies for infertility treatment. Methods Transcriptomic profiling of exosomes was performed to identify factors associated with endometrial receptivity. miR‐203a‐3p, exhibiting high expression levels in exosomes, was selected for further investigation. Human endometrial tissues from different menstrual phases and patient groups were analyzed for miR‐203a‐3p expression. Functional studies using miR‐203a‐3p mimics and engineered exosomes were conducted in non‐receptive AN3‐CA cells. Results During the secretory phase, miR‐203a‐3p expression was markedly higher in the endometria of fertile women than in those of infertile women. Overexpression of miR‐203a‐3p, which directly targeted Snail family transcriptional repressor (SNAI1), resulted in increased E‐cadherin expression and enhanced spheroid attachment in non‐receptive AN3‐CA cells. Consistently, delivery of miR‐203a‐3p mimics via engineered exosomes increased E‐cadherin expression by suppressing SNAI1 and enhanced spheroid adhesion in AN3‐CA cells. Conclusions Our data highlight the importance of the miR‐203a‐3p/SNAI1/E‐cadherin axis in governing endometrial receptivity. Exosome‐mediated delivery of miR‐203a‐3p mimics may represent a promising therapeutic strategy for improving embryo implantation and treating infertility.